Is DRC7 p.Ala769Val (c.2306C>T) pathogenic?

DRC7 p.Ala769Val (c.2306C>T) is classified Uncertain significance in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.1344); Rare (popmax 0.11%, sas).

How common is DRC7 p.Ala769Val (c.2306C>T) in the general population?

DRC7 p.Ala769Val (c.2306C>T) is rare (popmax 0.11%, sas) (gnomAD).

What do computational predictors say about DRC7 p.Ala769Val (c.2306C>T)?

AlphaMissense predicts likely benign (score 0.1344) — an in-silico prediction, not a clinical call.

DRC7 p.Ala769Val

c.2306C>T · rs373693140 · VCV3085757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1344 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1344	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.62, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% South Asian · 100/90,940 alleles

Filtering AF 0.0925% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.086%

Overall 0.0165% 266/1,612,100 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.11%	909
East Asian	0.078%	1,281
Remaining individualsnot grpmax-eligible	0.04%	2,498
Middle Eastern	0.0331%	3,018
Admixed American	0.0133%	7,491
European (non-Finnish)	0.0078%	12,822
African / African-American	0.00533%	18,749

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.Ala769Val
Coding: c.2306C>T
MANE Select: NM_001289162
dbSNP: rs373693140
Type: single nucleotide variant
Location: chr16:57728499 (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.Arg103His Uncertain significance ★ ⚠ same type
DRC7 p.Arg112His Uncertain significance ★ ⚠ same type
DRC7 p.Arg134Trp 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-ala769val (accessed [today's date]).

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