Is MVK p.Pro263Ser (c.787C>T) pathogenic?

MVK p.Pro263Ser (c.787C>T) is classified Uncertain significance in MVK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-07-01). AlphaMissense: likely benign (0.2379); Absent from gnomAD v4.1.

How common is MVK p.Pro263Ser (c.787C>T) in the general population?

MVK p.Pro263Ser (c.787C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MVK p.Pro263Ser (c.787C>T)?

AlphaMissense predicts likely benign (score 0.2379) — an in-silico prediction, not a clinical call.

MVK p.Pro263Ser

c.787C>T · rs1885665220 · VCV932337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2379 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2379	likely benign
REVEL	0.632	indeterminate
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 22 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	19.62	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

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: MVK
Protein: p.Pro263Ser
Coding: c.787C>T
MANE Select: NM_000431
dbSNP: rs1885665220
Type: single nucleotide variant
Location: chr12:109591259 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.31 · 1 PDB
Residue 263: an α-helix

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

Similar variants

MVK p.Pro263Arg Uncertain significance ★★ ⚠ same residue
MVK p.Pro263= Benign/Likely benign ★★ same residue
MVK c.1039+1G>C Likely pathogenic ★★ same type
MVK c.677+1G>A Likely pathogenic ★★ same type
MVK c.78+1G>A Likely pathogenic ★★ same type
MVK c.79-2A>G Likely pathogenic ★★ same type
MVK p.Ala147Thr Likely pathogenic ★★ same type
MVK p.Ala148Thr Pathogenic/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/mvk-p-pro263ser (accessed [today's date]).

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