Is MVD p.Pro396Gln (c.1187C>A) pathogenic?

MVD p.Pro396Gln (c.1187C>A) is classified Uncertain significance in MVD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: ambiguous (0.459); Very rare (popmax 0.00135%, afr).

How common is MVD p.Pro396Gln (c.1187C>A) in the general population?

MVD p.Pro396Gln (c.1187C>A) is very rare (popmax 0.00135%, afr) (gnomAD).

What do computational predictors say about MVD p.Pro396Gln (c.1187C>A)?

AlphaMissense predicts ambiguous (score 0.459) — an in-silico prediction, not a clinical call.

MVD p.Pro396Gln

c.1187C>A · VCV3400179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.459 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.459	ambiguous
REVEL	0.25	benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 11 kb · p 0.00014 · regional, not allelic
Overall
CADD	20.2	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 0.00135% African / African-American · 1/74,148 alleles

Overall 7.04e-05% 1/1,420,928 alleles · very rare

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.Pro396Gln
Coding: c.1187C>A
MANE Select: NM_002461
Type: single nucleotide variant
Location: chr16:88652541 (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.Pro396Arg 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-pro396gln (accessed [today's date]).

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