Is MSH3 p.Arg26Pro (c.77G>C) pathogenic?

MSH3 p.Arg26Pro (c.77G>C) is classified Uncertain significance in MSH3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-22). AlphaMissense: ambiguous (0.3764); Absent from gnomAD v4.1; Associated with endometrial carcinoma.

What condition is associated with MSH3 p.Arg26Pro (c.77G>C)?

MSH3 p.Arg26Pro (c.77G>C) is associated with endometrial carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Arg26Pro (c.77G>C) in the general population?

MSH3 p.Arg26Pro (c.77G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSH3 p.Arg26Pro (c.77G>C)?

AlphaMissense predicts ambiguous (score 0.3764) — an in-silico prediction, not a clinical call.

MSH3 p.Arg26Pro

c.77G>C · rs780517196 · VCV1464022

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3764 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

endometrial carcinoma

Computational evidence

Protein change
AlphaMissense	0.3764	ambiguous
REVEL	0.584	indeterminate
SaProt	LLR -11.91	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.1	GERP 0.96, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 221 kb · p 0.0024 · regional, not allelic
Overall
CADD	28.9	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: MSH3
Protein: p.Arg26Pro
Coding: c.77G>C
MANE Select: NM_000791 · reported on NM_002439
dbSNP: rs780517196
Type: single nucleotide variant
Location: chr5:80654804 (GRCh38)

Full MSH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

endometrial carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

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/msh3-p-arg26pro (accessed [today's date]).

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