Is MSH2 p.Val17= (c.51C>G) pathogenic?

MSH2 p.Val17= (c.51C>G) is classified Benign/Likely benign in MSH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-21). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH2 p.Val17= (c.51C>G)?

MSH2 p.Val17= (c.51C>G) is associated with hereditary neoplastic syndrome, Lynch syndrome 1 (ClinVar).

How common is MSH2 p.Val17= (c.51C>G) in the general population?

MSH2 p.Val17= (c.51C>G) is absent from gnomAD v4.1 (gnomAD).

MSH2 p.Val17=

c.51C>G · rs397515879 · VCV1136754

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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 carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.21	GERP -1.4, phastCons 0.008
Overall
CADD	11.4	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.Val17=
Coding: c.51C>G
MANE Select: NM_000251
dbSNP: rs397515879
Type: single nucleotide variant
Location: chr2:47403242 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 17: an α-helix; a UniProt-annotated variant site (in gastric cancer; uncertain significance; cryptic acceptor splice site suppressed on ex vivo splicing assay)

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

Also linked: Lynch syndrome 1

Similar variants

MSH2 p.Val17Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val17Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val17Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 c.1076+1G>A Pathogenic ★★★ same condition
MSH2 c.1076+1G>T Likely pathogenic ★★★ same condition
MSH2 c.1077-1G>C Likely pathogenic ★★★ same condition
MSH2 c.1077-1G>T Likely pathogenic ★★★ same condition
MSH2 c.1077-2A>C 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-val17 (accessed [today's date]).

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