Is VDAC2 p.Phe201Ile (c.601T>A) pathogenic?

VDAC2 p.Phe201Ile (c.601T>A) is classified Uncertain significance in VDAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.9757); Absent from gnomAD v4.1.

How common is VDAC2 p.Phe201Ile (c.601T>A) in the general population?

VDAC2 p.Phe201Ile (c.601T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about VDAC2 p.Phe201Ile (c.601T>A)?

AlphaMissense predicts likely pathogenic (score 0.9757) — an in-silico prediction, not a clinical call.

VDAC2 p.Phe201Ile

c.601T>A · VCV4198618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9757	likely pathogenic
REVEL	0.54	indeterminate
SaProt	LLR -12.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: VDAC2
Protein: p.Phe201Ile
Coding: c.601T>A
MANE Select: NM_001391963
Type: single nucleotide variant
Location: chr10:75222268 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.28 · 3 PDB
Residue 201: 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-phe201ile (accessed [today's date]).

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