Is VDAC2 p.Asp111Val (c.332A>T) pathogenic?

VDAC2 p.Asp111Val (c.332A>T) is classified Uncertain significance in VDAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: likely pathogenic (0.9179); Very rare (popmax 0.00402%, afr).

How common is VDAC2 p.Asp111Val (c.332A>T) in the general population?

VDAC2 p.Asp111Val (c.332A>T) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about VDAC2 p.Asp111Val (c.332A>T)?

AlphaMissense predicts likely pathogenic (score 0.9179) — an in-silico prediction, not a clinical call.

VDAC2 p.Asp111Val

c.332A>T · rs1272676234 · VCV2241313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9179	likely pathogenic
REVEL	0.648	pathogenic-leaning
SaProt	LLR -12.87	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 9.4	GERP 2.6, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 12 kb · p 9.4e-07 · regional, not allelic
Overall
CADD	26.3	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 0.00402% African / African-American · 3/74,700 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000496%

Overall 0.000187% 3/1,600,878 alleles · very rare exomes 2/1,448,642 · genomes 1/152,236 · 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: VDAC2
Protein: p.Asp111Val
Coding: c.332A>T
MANE Select: NM_001391963
dbSNP: rs1272676234
Type: single nucleotide variant
Location: chr10:75219332 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.28 · 3 PDB
Residue 111: a β-strand

Full VDAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VDAC2 p.Asn196= Benign ★★ same type
VDAC2 c.31+411A>G Uncertain significance ★ same type
VDAC2 c.31+413C>G Uncertain significance ★ same type
VDAC2 c.31+419T>A Uncertain significance ★ same type
VDAC2 c.31+421G>T Uncertain significance ★ same type
VDAC2 c.736-1G>A Uncertain significance ★ same type
VDAC2 p.Ala19Val Uncertain significance ★ ⚠ same type
VDAC2 p.Ala281Thr 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/vdac2-p-asp111val (accessed [today's date]).

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