Is DRC10 p.Val105Ile (c.313G>A) pathogenic?

DRC10 p.Val105Ile (c.313G>A) is classified Uncertain significance in DRC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.0805); Very rare (popmax 0.00667%, amr).

How common is DRC10 p.Val105Ile (c.313G>A) in the general population?

DRC10 p.Val105Ile (c.313G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about DRC10 p.Val105Ile (c.313G>A)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

DRC10 p.Val105Ile

c.313G>A · rs373805294 · VCV2235929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.62	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 -3.4	GERP -4.7
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.015 · regional, not allelic
Overall
CADD	0.074	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 0.00667% Admixed American · 4/59,994 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00458% 74/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,999
European (non-Finnish)	0.00542%	18,438
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,890
South Asian	0.0022%	45,545
Finnishnot grpmax-eligible	0.00156%	64,008

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.Val105Ile
Coding: c.313G>A
MANE Select: NM_001330452
dbSNP: rs373805294
Type: single nucleotide variant
Location: chr12:113207854 (GRCh38)
Structure: AlphaFold pLDDT 82.03 · 1 PDB

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.Ala403Val 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

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-val105ile (accessed [today's date]).

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