Is DRC10 p.Ala403Val (c.1208C>T) pathogenic?

DRC10 p.Ala403Val (c.1208C>T) is classified Uncertain significance in DRC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely pathogenic (0.7572); Rare (popmax 0.116%, mid).

How common is DRC10 p.Ala403Val (c.1208C>T) in the general population?

DRC10 p.Ala403Val (c.1208C>T) is rare (popmax 0.116%, mid) (gnomAD).

What do computational predictors say about DRC10 p.Ala403Val (c.1208C>T)?

AlphaMissense predicts likely pathogenic (score 0.7572) — an in-silico prediction, not a clinical call.

DRC10 p.Ala403Val

c.1208C>T · rs561746821 · VCV2509940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7572 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7572	likely pathogenic · top 8% in DRC10
REVEL	0.346	indeterminate
SaProt	LLR -11.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.015 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.116% Middle Eastern · 7/6,060 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.0113% 183/1,613,738 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	866
Admixed American	0.035%	2,855
Remaining individualsnot grpmax-eligible	0.0224%	4,464
African / African-American	0.0147%	6,811
European (non-Finnish)	0.0103%	9,752
South Asian	0.00878%	11,384
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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: DRC10
Protein: p.Ala403Val
Coding: c.1208C>T
MANE Select: NM_001330452
dbSNP: rs561746821
Type: single nucleotide variant
Location: chr12:113195717 (GRCh38)
Structure: AlphaFold pLDDT 82.03 · 1 PDB
Residue 403: the iq domain

Full DRC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC10 p.Ala31Thr Uncertain significance ★ ⚠ same type
DRC10 p.Ala393Ser Uncertain significance ★ ⚠ same type
DRC10 p.Ala404Thr Uncertain significance ★ ⚠ same type
DRC10 p.Ala59Val Uncertain significance ★ ⚠ same type
DRC10 p.Arg191Cys Uncertain significance ★ ⚠ same type
DRC10 p.Arg399Gly Uncertain significance ★ ⚠ same type
DRC10 p.Arg426Gln Uncertain significance ★ ⚠ same type
DRC10 p.Gln172Pro 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/drc10-p-ala403val (accessed [today's date]).

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