Is MSH3 p.Ala58Pro (c.172G>C) pathogenic?

MSH3 p.Ala58Pro (c.172G>C) is classified Benign in MSH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-07). AlphaMissense: likely benign (0.0847); Very rare (popmax 0.00869%, afr).

How common is MSH3 p.Ala58Pro (c.172G>C) in the general population?

MSH3 p.Ala58Pro (c.172G>C) is very rare (popmax 0.00869%, afr) (gnomAD).

What do computational predictors say about MSH3 p.Ala58Pro (c.172G>C)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

MSH3 p.Ala58Pro

c.172G>C · rs148550291 · VCV759929

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00869%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Regional constraint	o/e 1.08	unconstrained · MANE · 221 kb · p 0.0024 · regional, not allelic
Overall
CADD	11.72	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 0.00869% African / African-American · 4/46,014 alleles

Filtering AF 0.00293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.000881% 13/1,474,790 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00869%	11,503
East Asian	0.00518%	19,309
Remaining individualsnot grpmax-eligible	0.00171%	58,442
European (non-Finnish)	0.000536%	186,406

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: MSH3
Protein: p.Ala58Pro
Coding: c.172G>C
MANE Select: NM_000791 · reported on NM_002439
dbSNP: rs148550291
Type: single nucleotide variant
Location: chr5:80654899 (GRCh38)

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

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-ala58pro (accessed [today's date]).

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