Is DRC7 p.Asp321His (c.961G>C) pathogenic?

DRC7 p.Asp321His (c.961G>C) is classified Uncertain significance in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.7538); Very rare (popmax 0.00167%, amr).

How common is DRC7 p.Asp321His (c.961G>C) in the general population?

DRC7 p.Asp321His (c.961G>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DRC7 p.Asp321His (c.961G>C)?

AlphaMissense predicts likely pathogenic (score 0.7538) — an in-silico prediction, not a clinical call.

DRC7 p.Asp321His

c.961G>C · VCV3842446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7538	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 0.000137% 2/1,461,274 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	8.47e-05%	1,180,006

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DRC7
Protein: p.Asp321His
Coding: c.961G>C
MANE Select: NM_001289162
Type: single nucleotide variant
Location: chr16:57707562 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 1 PDB

Full DRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC7 p.Ala510Pro Uncertain significance ★ ⚠ same type
DRC7 p.Ala605Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala629Thr Uncertain significance ★ ⚠ same type
DRC7 p.Ala65Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala709Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala769Val Uncertain significance ★ ⚠ same type
DRC7 p.Arg103His Uncertain significance ★ ⚠ same type
DRC7 p.Arg112His Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/drc7-p-asp321his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown