Is MSH2 p.Val63fs (c.186_187del) pathogenic?

MSH2 p.Val63fs (c.186187del) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-08). Associated with colorectal cancer.

What condition is associated with MSH2 p.Val63fs (c.186_187del)?

MSH2 p.Val63fs (c.186_187del) is associated with colorectal cancer (ClinVar).

MSH2 p.Val63fs

c.186_187del · VCV4681188

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

colorectal cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MSH2
Protein: p.Val63fs
Coding: c.186_187del
MANE Select: NM_000251
Type: Deletion
Location: chr2:47403374 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB

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

Disease context

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSH2 p.Val63Ala Uncertain significance ★★ ⚠ same residue
MSH2 p.Val63Glu Uncertain significance ★★ ⚠ same residue
MSH2 p.Val63Met Uncertain significance ★★ ⚠ same residue
MSH2 p.Val63Leu Uncertain significance ★ ⚠ same residue
MSH2 p.Val63= Likely benign ★ same residue
MSH2 p.Ala15fs Pathogenic same condition
MSH2 p.His785Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
MSH2 c.1077-?_1386+?del 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-val63fs (accessed [today's date]).

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