Is DRC11 p.Ala735Val (c.2204C>T) pathogenic?

DRC11 p.Ala735Val (c.2204C>T) is classified Uncertain significance in DRC11 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.6205); Very rare (popmax 0.00446%, eas).

How common is DRC11 p.Ala735Val (c.2204C>T) in the general population?

DRC11 p.Ala735Val (c.2204C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DRC11 p.Ala735Val (c.2204C>T)?

AlphaMissense predicts likely pathogenic (score 0.6205) — an in-silico prediction, not a clinical call.

DRC11 p.Ala735Val

c.2204C>T · rs750101433 · VCV2609633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6205	likely pathogenic
REVEL	0.708	pathogenic-leaning
SaProt	LLR -10.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 183 kb · p 0.19 · regional, not allelic
Overall
CADD	26.1	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 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000496% 8/1,613,744 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
Admixed American	0.00167%	59,988
Finnishnot grpmax-eligible	0.00156%	63,998
African / African-American	0.00134%	74,868
European (non-Finnish)	0.000254%	393,292

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: DRC11
Protein: p.Ala735Val
Coding: c.2204C>T
MANE Select: NM_024726
dbSNP: rs750101433
Type: single nucleotide variant
Location: chr2:236331528 (GRCh38)
Structure: AlphaFold pLDDT 79.87 · 1 PDB

Full DRC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC11 p.Ala143Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala574Pro Uncertain significance ★ ⚠ same type
DRC11 p.Ala594Val Uncertain significance ★ ⚠ same type
DRC11 p.Ala804Gly Uncertain significance ★ ⚠ same type
DRC11 p.Ala806Val Uncertain significance ★ ⚠ same type
DRC11 p.Arg224His Uncertain significance ★ ⚠ same type
DRC11 p.Arg531Cys Uncertain significance ★ ⚠ same type
DRC11 p.Arg626Gln 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/drc11-p-ala735val (accessed [today's date]).

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