Is MSH2 p.Ser77= (c.231T>C) pathogenic?

MSH2 p.Ser77= (c.231T>C) is classified Likely benign in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). Absent from gnomAD v4.1.

How common is MSH2 p.Ser77= (c.231T>C) in the general population?

MSH2 p.Ser77= (c.231T>C) is absent from gnomAD v4.1 (gnomAD).

MSH2 p.Ser77=

c.231T>C · VCV3895879

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.84	GERP 0.19, phastCons 1
Overall
CADD	9.176	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: MSH2
Protein: p.Ser77=
Coding: c.231T>C
MANE Select: NM_000251
Type: single nucleotide variant
Location: chr2:47408420 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 77: a β-strand

Full MSH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MSH2 p.Ser77Arg Uncertain significance ★★ ⚠ same residue
MSH2 p.Ser77Gly Uncertain significance ★★ ⚠ same residue
MSH2 p.Ser77Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ser77Cys Uncertain significance ★ ⚠ same residue
MSH2 p.Ser77Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ser77fs Pathogenic ★★★ same residue
MSH2 c.1076+1G>A Pathogenic ★★★ same type
MSH2 c.1076+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/msh2-p-ser77 (accessed [today's date]).

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