Is MSH2 p.Val161= (c.483T>A) pathogenic?

MSH2 p.Val161= (c.483T>A) is classified Likely benign in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-16). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH2 p.Val161= (c.483T>A)?

MSH2 p.Val161= (c.483T>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Val161= (c.483T>A) in the general population?

MSH2 p.Val161= (c.483T>A) is absent from gnomAD v4.1 (gnomAD).

MSH2 p.Val161=

c.483T>A · rs375202935 · VCV1743499

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.54	donor gain · deltas
Pangolin	Δ0.60	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -8	GERP -3.5
Overall
CADD	14.54	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.Val161=
Coding: c.483T>A
MANE Select: NM_000251
dbSNP: rs375202935
Type: single nucleotide variant
Location: chr2:47410210 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 161: a β-strand; a UniProt-annotated variant site (in lynch1; decreased mismatch repair activity; affects protein stability; loss of protein expression)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSH2 p.Val161Asp Pathogenic ★★★ same residue
MSH2 p.Val161Gly Uncertain significance ★★ ⚠ same residue
MSH2 p.Val161Phe Uncertain significance ★★ ⚠ same residue
MSH2 p.Val161Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val161Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val161Leu Uncertain significance ★ ⚠ same residue
MSH2 c.1076+1G>A Pathogenic ★★★ same condition
MSH2 c.1076+1G>T Likely pathogenic ★★★ same condition

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-val161 (accessed [today's date]).

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