Is MSH2 p.Val437= (c.1311G>T) pathogenic?

MSH2 p.Val437= (c.1311G>T) is classified Benign/Likely benign in MSH2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-14). Very rare (popmax 0.000678%, nfe); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH2 p.Val437= (c.1311G>T) in the general population?

MSH2 p.Val437= (c.1311G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

MSH2 p.Val437=

Q: What condition is associated with MSH2 p.Val437= (c.1311G>T)?

MSH2 p.Val437= (c.1311G>T) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, Lynch syndrome 1 (ClinVar).

c.1311G>T · rs730881781 · VCV182603

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.4, phastCons 1
Overall
CADD	6.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,638 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,328 alleles · very rare exomes 8/1,461,062 · genomes 0/152,266 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MSH2
Protein: p.Val437=
Coding: c.1311G>T
MANE Select: NM_000251
dbSNP: rs730881781
Type: single nucleotide variant
Location: chr2:47445582 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 437: 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

Also linked: Lynch syndrome Lynch syndrome 1 hereditary neoplastic syndrome

Similar variants

MSH2 p.Val437Met Uncertain significance ★★ ⚠ same residue
MSH2 p.Val437Ala Uncertain significance ★ ⚠ same residue
MSH2 p.Val437Leu Uncertain significance ★ ⚠ same residue
MSH2 p.Val437Glu Likely benign ★ same residue
MSH2 p.Val437fs Pathogenic ★ same residue
MSH2 p.Val437_Thr438insMet 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-val437 (accessed [today's date]).

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