gnomAD (Genome Aggregation Database)

Largest public database of human genetic variation. Contains allele frequencies from 807,162 individuals (v4.1). Essential for PM2 (absence) evidence in ACMG classification.

What It Does

Population allele frequencies across diverse ancestries
Coverage statistics per position
Constraint metrics (pLI, LOEUF, missense Z) per gene
Loss-of-function variant counts
Structural variants (SVs)

How to Use

Web

Go to https://gnomad.broadinstitute.org
Search gene “STRC” or variant “15-43600551-A-C”
Check allele frequency, ancestry breakdown, and constraint

API

# GraphQL API
curl -X POST https://gnomad.broadinstitute.org/api \
  -H "Content-Type: application/json" \
  -d '{"query": "{ gene(gene_symbol: \"STRC\", reference_genome: GRCh38) { gnomad_constraint { pLI oe_lof } } }"}'

Python (Hail)

import hail as hl
# Load gnomAD dataset (requires Hail setup)
gnomad = hl.read_table("gs://gcp-public-data--gnomad/release/4.1/ht/genomes/gnomad.genomes.v4.1.sites.ht")

Verified Status

VERIFIED — STRC E1659A (c.4976A>C) is ABSENT from gnomAD (0/251,000+ alleles). This confirms PM2_Supporting evidence.

STRC Research Usage

STRC E1659A Conservation and Reclassification — PM2 evidence (absent)
STRC Variant c.4976A>C — Misha — population frequency check
STRC gene constraint: moderate (some LoF variants exist — consistent with recessive disease)

Critical Notes

STRC has known issues in gnomAD due to pseudogene (STRCP1) read mismapping
Coverage may be low at STRC locus — check coverage statistics
Structural variants — the 98kb deletion may or may not be in gnomAD SVs

Results (April 2026)

STRC constraint scores: pLI = 0.14 (tolerant to LoF — consistent with recessive disease), missense Z-score = 7.62 (HIGHLY constrained for missense). This means STRC tolerates loss-of-function (one broken copy is fine = recessive) but missense variants are under strong selection.
Still untapped: ancestry-specific frequencies, SV database search for 98kb deletion

Connections

ClinVar [see-also] — variant classification
seqr [see-also] — rare disease analysis (uses gnomAD)
STRC E1659A Conservation and Reclassification [used-in]
STRC Pseudogene Problem [see-also] — affects gnomAD read mapping

STRC Research

Explorer

gnomAD