Is MSH2 p.Glu467= (c.1401A>G) pathogenic?

MSH2 p.Glu467= (c.1401A>G) is classified Benign/Likely benign in MSH2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-02). Very rare (popmax 0.0022%, nfe); Associated with mismatch repair cancer syndrome 2.

What condition is associated with MSH2 p.Glu467= (c.1401A>G)?

MSH2 p.Glu467= (c.1401A>G) is associated with mismatch repair cancer syndrome 2, Lynch syndrome, Lynch syndrome 1 (ClinVar).

How common is MSH2 p.Glu467= (c.1401A>G) in the general population?

MSH2 p.Glu467= (c.1401A>G) is very rare (popmax 0.0022%, nfe) (gnomAD).

MSH2 p.Glu467=

Q: How is Constitutional mismatch repair deficiency syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1401A>G · rs1558508085 · VCV630995

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Conditions

mismatch repair cancer syndrome 2

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 2.3	GERP -1.7, phastCons 1
Overall
CADD	5.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,179,896 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00161% 26/1,613,938 alleles · very rare exomes 26/1,461,618 · genomes 0/152,320 · 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.Glu467=
Coding: c.1401A>G
MANE Select: NM_000251
dbSNP: rs1558508085
Type: single nucleotide variant
Location: chr2:47463045 (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

mismatch repair cancer syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome Lynch syndrome 1 Muir-Torre syndrome hereditary neoplastic syndrome

For Constitutional mismatch repair deficiency syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

MSH2 p.Glu467Ter Pathogenic ★★★ same residue
MSH2 p.Glu467Lys Uncertain significance ★★ ⚠ same residue
MSH2 p.Glu467fs Pathogenic ★ same residue
MSH2 p.Glu467Ala Uncertain significance ★ ⚠ 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

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-glu467 (accessed [today's date]).

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