The commonest G6PD-deficiency variant in populations of African ancestry. ClinVar classifies it Pathogenic/Likely pathogenic.

establisheduntested in South Asian studies

Carried here as a deliberate negative. In gnomAD v4 this variant is at 0.00030 in South Asians and 0.12277 in Africans — a 400-fold difference — while the Mediterranean variant on the row above runs the other way, 0.019 against 0.0002. A G6PD panel built on the well-known African variant would miss almost every deficient South Asian and would look like a working panel while doing it. That is the same failure as reporting lactase persistence from one European SNP, in a gene where the consequence is a drug reaction.

This variant reduces glucose-6-phosphate dehydrogenase activity and is the commonest cause of G6PD deficiency reported in Indian populations. ClinVar classifies it Pathogenic/Likely pathogenic for G6PD deficiency.

establishedreplicated in South Asian studies

G6PD deficiency is diagnosed by an enzyme activity test, not by a genotype. This tells you a variant is present. It is also not the only cause of G6PD deficiency, and the others are not read by this file. Measured as readable: the GSA probe here is [A/G] on the plus strand, which interrogates the correct alternate, and the site is present in every real 23andMe and AncestryDNA file tested.

A variant reducing glucose-6-phosphate dehydrogenase activity, classified Pathogenic/Likely pathogenic in ClinVar, and the most frequently reported cause of G6PD deficiency in Indian series.

establishedreplicated in South Asian studies

The measurement worth quoting precisely, because it is easy to misread. Among 350 molecularly characterised G6PD-deficient individuals drawn from a screen of 20,896 people across India, this variant accounted for 56.5% of deleterious alleles and the Mediterranean variant for 23.6%. That is a share of the alleles found IN DEFICIENT PEOPLE, not a frequency in the population — overall deficiency prevalence in the same screen was 1.9%, ranging 0.8 to 6.3% by region. The two numbers answer different questions and only the second says how common deficiency is.

A variant in the HBB transcription start region, classified Pathogenic/Likely pathogenic in ClinVar, and reported in Indian series as a mild beta-thalassemia allele.

establishedreplicated in South Asian studies

Reported in the literature as producing a milder phenotype than the splice-site and nonsense alleles, which is a statement about published series and not a prediction about any individual.

A nonsense variant in HBB, classified Pathogenic in ClinVar, and one of the beta-thalassemia alleles reported in Indian series.

establishedreplicated in South Asian studies

Two limits. This site is absent from the base Illumina GSA manifest and present in all three real 23andMe v5 files, because 23andMe adds custom content on top of the GSA platform and does not publish its site list — so the probe alleles here are unknown and unknowable from any source we are willing to use. It is also a T/A pair, which is strand-ambiguous, and until now we discarded such sites rather than resolve them — our policy rather than a limit of the array, whose three designs state the strand unanimously here. The row declines rather than reporting an absence.

A variant at the codon 30 splice junction of HBB, classified Pathogenic in ClinVar and reported in Indian beta-thalassemia series.

establishedreplicated in South Asian studies

Two independent limits. ClinVar records two further pathogenic alleles at this coordinate, so an array whose probe reads one of those has said nothing about ours, and the row never reports an absence here. It is also a C/G pair, which is strand-ambiguous; whether the probe designs at this position state a strand unanimously has not been measured, so the drop is attributed to our own policy rather than to the array until it is.

A splice-donor variant in HBB, classified Pathogenic in ClinVar, and among the beta-thalassemia alleles most frequently reported in Indian series after IVS1-5.

establishedreplicated in South Asian studies

Three separate pathogenic alleles sit at this coordinate, so an array whose probe reads a different one has said nothing about this variant. The row therefore never reports an absence here.

A splice-site variant in HBB, classified Pathogenic in ClinVar, and the most frequently reported beta-thalassemia allele in Indian series.

establishedreplicated in South Asian studies

Whether this variant can be read from a consumer array is unknown, and that is the honest answer rather than a hedge. Three different pathogenic alleles share this rsID at chr11:5226925 — C>A, C>G and C>T are separate ClinVar records — and the Illumina GSA manifest carries four probe designs at the position, one of which does interrogate C>G. Which design a vendor actually shipped is not stated in the file, which names the marker plainly with no suffix. So the site is typed, and what was typed cannot be determined.

The HBB variant that produces haemoglobin S, classified Pathogenic in ClinVar for sickle cell disease.

establishedreplicated in South Asian studies

Not typed by 23andMe v5 at all — absent from all three real files tested, while present in a 2023 AncestryDNA file. So whether this row can be answered depends on which vendor and which chip version produced the upload, and the answer has to be computed per file rather than stated per vendor. It is also a T/A pair, which is strand-ambiguous, and unlike the other rows here the three probe designs at this position disagree about which strand they read, so no declaration exists to resolve it against. That is a limit of the array rather than a policy of ours.

A splice-site change that produces no working CYP2C19 enzyme from the affected copy. CYP2C19 converts several drugs into their active form, so carrying two copies means the enzyme activity is absent rather than reduced.

establishedreplicated in South Asian studies

This is not medical advice, and not a reason to change any medicine. If a doctor has prescribed something, keep taking it and show them this page. Metaboliser status is assigned from a person's full CYP2C19 star-allele diplotype; this file reads two of those alleles, so a result here is partial. Genotype is also not a measurement of enzyme activity, which is what a clinical test would give you.

A premature stop codon that truncates the CYP2C19 protein. Same consequence as *2 -- no working enzyme from that copy -- by a different mechanism.

establishedreplicated in South Asian studies

Not medical advice. Much rarer than *2 in South Asians -- gnomAD puts it at 0.5% against 33% -- so for most readers the *2 row is the informative one. A full diplotype needs more alleles than this file reads.

Increases CYP2C19 activity, the opposite direction to the *2 and *3 variants already in this report. The Clinical Pharmacogenetics Implementation Consortium publishes prescribing guidance based on the combination of these variants; this report shows what was found and does not adjust any dose.

establisheduntested in South Asian studies

The prescribing guidance behind this variant is built mainly on European and East Asian cohorts. Its frequency and effect in South Asians are less well measured.

The R139C change reduces NUDT15 enzyme activity, so an active metabolite the enzyme normally clears persists longer. CPIC assigns metaboliser status from NUDT15 and TPMT together.

establishedreplicated in South Asian studies

Not medical advice, and not a reason to stop or change any medicine. Stopping a prescribed treatment is more dangerous than any genotype on this page. Show this to the prescribing doctor and let them decide. This variant is roughly 24 times commoner in South Asians than in Europeans, which is why it is here and why guidance derived from European cohorts has historically under-served this population.

TPMT is the second enzyme CPIC reads alongside NUDT15. The *3C allele reduces its activity.

establisheduntested in South Asian studies

Not medical advice. TPMT*3C is one of several TPMT alleles and this file reads one of them, so a normal result here does not establish normal TPMT activity. Enzyme activity is measurable directly and that test, not this one, is what a clinic would use. No South Asian cohort study of this allele's effect is cited here -- the frequency data below is South Asian, the effect evidence is not.

SLCO1B1 is a liver transporter: it moves certain compounds out of the blood and into hepatocytes, where they act and are cleared. The V174A change reduces that transport, so what the transporter handles stays in circulation longer.

establisheduntested in South Asian studies

Not medical advice, and not a reason to stop or change any medicine. Stopping a prescribed treatment on the basis of a web page is more dangerous than anything this row describes. The variant is LESS common in South Asians than in Europeans -- 4.9% against 15.9% -- so for most readers here this row will be uninformative. Effect evidence is European; no South Asian cohort is cited.

This promoter variant lowers how much VKORC1 enzyme the liver produces. VKORC1 is the target of one class of anticoagulant, so the amount present matters to anyone taking one.

establisheduntested in South Asian studies

Not medical advice. Anticoagulant dosing is managed by blood tests that measure the actual effect in the actual person, which is far more informative than any genotype. Never change a dose on the basis of this page. Effect evidence is largely European and East Asian; no South Asian cohort is cited here.

The commonest ASPA variant in Canavan disease, a recessive condition affecting the white matter of the brain. ClinVar classifies it Pathogenic/Likely pathogenic.

establisheduntested in South Asian studies

This variant's frequency has not been measured in South Asian populations. The Canavan literature is largely Ashkenazi Jewish, where it is commonest; what carrier frequency looks like in South Asia is not something this report can tell you.

The C allele abolishes Duffy antigen expression on red cells. It confers resistance to Plasmodium vivax malaria and is associated with a lower baseline neutrophil count that is benign -- 'benign ethnic neutropenia'.

establisheduntested in South Asian studies

The clinically important part is the neutrophil count, because a normal result for a Duffy-null person can be read as abnormal against a reference range built on people who are not. This is close to fixed in West African populations, absent in the South Asian and East Asian cohorts, and is on the panel because the report is global.

The commonest cause of hereditary haemochromatosis, in which the body absorbs more iron than it needs. ClinVar classifies it Pathogenic.

establisheduntested in South Asian studies

Almost all HFE research is in European-ancestry cohorts, where this variant is commonest. It is rare in South Asians and its frequency there is not well measured, so an absence here says less than it would for a European genome.

A second HFE change described in the same 1996 paper as C282Y. It is common in many populations and, on its own, is not generally associated with iron overload; the combination most reported is one copy of this alongside one copy of C282Y.

moderateuntested in South Asian studies

ClinVar records conflicting classifications for this variant, and it is reported far more often than iron overload occurs, so it is shown as a finding rather than a conclusion. Its frequency in South Asians is not well measured.

The T allele reduces ABCG2 transporter function. It is associated with higher serum urate and with reduced response to allopurinol, and CPIC uses it in guidance on rosuvastatin dosing.

establisheduntested in South Asian studies

Urate and gout have large dietary and renal components that this variant does not read. The allopurinol association describes response at a given dose rather than whether the drug works.

CYP2C9*3 substantially reduces enzyme activity. CPIC guidelines use CYP2C9 genotype in dosing recommendations for warfarin and for phenytoin.

establisheduntested in South Asian studies

A genotype is not a dose. CPIC recommendations combine CYP2C9 with VKORC1 and with clinical factors, and warfarin is titrated on INR measurement whatever the genotype says. Carrying *3 is a reason to expect a lower dose requirement, not a reason to change one.

Genotype at this locus predicts response to interferon-based hepatitis C therapy and spontaneous clearance of the virus. The C allele is the favourable one; the T allele is associated with poorer response.

establisheduntested in South Asian studies

This is a variant whose clinical relevance has largely PASSED. Interferon-based regimens have been superseded by direct-acting antivirals, which cure across genotypes, and it is reported here as a well-established association rather than as a treatment decision anybody should now make.

The commonest reason CYP3A5 produces no working enzyme. It is the main genetic factor in tacrolimus dosing after transplantation.

establisheduntested in South Asian studies

Frequencies for this variant differ sharply between populations, and the South Asian estimate is less well measured than the European and African ones.