Is MVD p.Val232Met (c.694G>A) pathogenic?

MVD p.Val232Met (c.694G>A) is classified Uncertain significance in MVD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.1156); Ultra-rare (popmax 0.0267%, amr).

How common is MVD p.Val232Met (c.694G>A) in the general population?

MVD p.Val232Met (c.694G>A) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about MVD p.Val232Met (c.694G>A)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

MVD p.Val232Met

c.694G>A · rs749607828 · VCV2454915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -11.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -2.3, phastCons 0.11
Regional constraint	o/e 1.16	unconstrained · MANE · 11 kb · p 0.00014 · regional, not allelic
Overall
CADD	16.05	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 0.0267% Admixed American · 15/56,088 alleles

Filtering AF 0.0164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.00209% 33/1,580,172 alleles · ultra-rare exomes 25/1,427,914 · genomes 8/152,258 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,739
East Asian	0.00922%	10,845
African / African-American	0.00403%	24,796
South Asian	0.00345%	28,987
Finnishnot grpmax-eligible	0.00178%	56,230
European (non-Finnish)	0.0006%	166,639

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: MVD
Protein: p.Val232Met
Coding: c.694G>A
MANE Select: NM_002461
dbSNP: rs749607828
Type: single nucleotide variant
Location: chr16:88655402 (GRCh38)
Gene constraint: LOEUF 1.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.52 · 1 PDB

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

Similar variants

MVD p.Val232Leu Uncertain significance ★ ⚠ same residue
MVD p.Phe249Ser Pathogenic ★★ same type
MVD p.Thr120Met Uncertain significance ★★ ⚠ same type
MVD p.Arg78= Benign ★★ same type
MVD p.Lys368= Benign/Likely benign ★★ same type
MVD p.Pro77= Benign ★★ same type
MVD c.1013+1G>T Pathogenic ★ same type
MVD c.1014-1G>T Likely pathogenic ★ 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/mvd-p-val232met (accessed [today's date]).

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