Is DRC11 p.Asp299Val (c.896A>T) pathogenic?

DRC11 p.Asp299Val (c.896A>T) is classified Uncertain significance in DRC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely benign (0.2566); Very rare (popmax 6.2e-05%).

How common is DRC11 p.Asp299Val (c.896A>T) in the general population?

DRC11 p.Asp299Val (c.896A>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about DRC11 p.Asp299Val (c.896A>T)?

AlphaMissense predicts likely benign (score 0.2566) — an in-silico prediction, not a clinical call.

DRC11 p.Asp299Val

c.896A>T · rs1021644600 · VCV2291180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2566 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2566	likely benign
REVEL	0.763	pathogenic-leaning
SaProt	LLR -9.55	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 183 kb · p 0.19 · regional, not allelic
Overall
CADD	23.2	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 6.2e-05%

Overall 6.2e-05% 1/1,613,998 alleles · very rare exomes 1/1,461,686 · genomes 0/152,312 · joint denominator

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.Asp299Val
Coding: c.896A>T
MANE Select: NM_024726
dbSNP: rs1021644600
Type: single nucleotide variant
Location: chr2:236465535 (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.Ala735Val 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

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-asp299val (accessed [today's date]).

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