Your variants, consulted against the scientific record.

ClinVar classification

Pathogenic (3★ review status)

Variation ID

VCV000055407

ACMG criteria

PVS1, PM2, PP5

Classification

Class 5 (Pathogenic)

gnomAD v4.1 frequency

0.00012% (global)

Population context

Founder variant in specific populations (see literature citations)

Literature

Struewing et al. 1997 (NEJM); Hartman et al. 2012 (BRCA1 founder mutations)

Frameshift variant in BRCA1 exon 20. Predicted to cause loss of function via nonsense-mediated decay. One of three Ashkenazi Jewish founder mutations. Flagged for physician review under ACMG guidelines.

PharmGKB annotation

Level 1A

Allele function

No function

Metabolizer status

Intermediate (*1/*2) or Poor (*2/*2)

gnomAD v4.1 frequency

15.1% (global)

Population context

20–25% in East Asian populations

Clinical guidelines

CPIC (clopidogrel, PPIs, voriconazole, SSRIs)

Most common CYP2C19 loss-of-function variant. Associated with altered metabolism of multiple medications. CPIC guidelines recommend alternative therapy or dose adjustment for affected individuals. Flagged for physician awareness during prescribing decisions.

ClinVar classification

Benign / Risk factor (conflicting interpretations, reviewed)

gnomAD v4.1 frequency

32% heterozygous, 9% homozygous (global)

Enzyme activity

~65% (heterozygous), ~30% (homozygous)

Clinical relevance

Limited evidence for most claimed associations

High-frequency common variant extensively studied but with limited clinical significance for most claimed associations. Modest effect on folate metabolism. Atlas Delphi reports population frequency context to help distinguish common variants from actionable findings. Included here to illustrate how the report handles variants that are frequently overinterpreted online.