Is MVD p.Ala176= (c.528C>T) pathogenic?

MVD p.Ala176= (c.528C>T) is classified Likely benign in MVD (ClinVar, Single submitter, 2 submitters; last evaluated 2024-04-01). Rare (popmax 0.794%, afr).

How common is MVD p.Ala176= (c.528C>T) in the general population?

MVD p.Ala176= (c.528C>T) is rare (popmax 0.794%, afr) (gnomAD).

MVD p.Ala176=

c.528C>T · rs57279356 · VCV3040032

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.794%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.2
Overall
CADD	0.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.794% African / African-American · 596/75,016 alleles

Filtering AF 0.742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.721%

Overall 0.0403% 646/1,601,834 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.794%	126
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.024%	4,161
European (non-Finnish)	0.00161%	62,100
South Asian	0.0011%	91,078

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.Ala176=
Coding: c.528C>T
MANE Select: NM_002461
dbSNP: rs57279356
Type: single nucleotide variant
Location: chr16:88656180 (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.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
MVD p.Asn292Ser 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-ala176 (accessed [today's date]).

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