Is MSH2 p.Pro439fs (c.1314_1315dup) pathogenic?

MSH2 p.Pro439fs (c.13141315dup) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Pro439fs (c.1314_1315dup)?

MSH2 p.Pro439fs (c.1314_1315dup) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

MSH2 p.Pro439fs

c.1314_1315dup · VCV3729155

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Hereditary nonpolyposis colorectal neoplasms

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 8 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.64, phastCons 1

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

Variant & gene context

Gene: MSH2
Protein: p.Pro439fs
Coding: c.1314_1315dup
MANE Select: NM_000251
Type: Duplication
Location: chr2:47445583 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 439: an α-helix

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

Disease context

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

Similar variants

MSH2 p.Pro439_Asp442del Pathogenic ★ same residue
MSH2 p.Pro439Arg Uncertain significance ★ ⚠ same residue
MSH2 p.Pro439Thr Uncertain significance ★ ⚠ same residue
MSH2 c.1076+1dup Likely pathogenic ★★ same condition
MSH2 p.Ala305fs Pathogenic ★★ same condition
MSH2 p.Arg219fs Pathogenic ★★ same condition
MSH2 p.Asp386fs Pathogenic ★★ same condition
MSH2 p.Asp442Ter 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-pro439fs (accessed [today's date]).

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