Is MSH3 p.Ala776= (c.2328T>C) pathogenic?

MSH3 p.Ala776= (c.2328T>C) is classified Likely benign in MSH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). Absent from gnomAD v4.1.

How common is MSH3 p.Ala776= (c.2328T>C) in the general population?

MSH3 p.Ala776= (c.2328T>C) is absent from gnomAD v4.1 (gnomAD).

MSH3 p.Ala776=

c.2328T>C · rs1580045459 · VCV2811841

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.37	GERP -0.56, phastCons 1
Overall
CADD	8.341	PHRED · no single calibrated threshold — expert panels disagree

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.Ala776=
Coding: c.2328T>C
MANE Select: NM_002439
dbSNP: rs1580045459
Type: single nucleotide variant
Location: chr5:80778729 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 776: a turn

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

Similar variants

MSH3 p.Ala776Asp Uncertain significance ★★ ⚠ same residue
MSH3 p.Ala776Pro Uncertain significance ★★ ⚠ same residue
MSH3 p.Ala776Val Uncertain significance ★★ ⚠ same residue
MSH3 p.Ala776Ser Uncertain significance ★ ⚠ same residue
MSH3 p.Ala776Thr Uncertain significance ★ ⚠ same residue
MSH3 c.1341-2A>C Likely pathogenic ★★ same type
MSH3 c.1341-2A>G Likely pathogenic ★★ same type
MSH3 c.1568+1G>A 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/msh3-p-ala776 (accessed [today's date]).

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