Is MSH2 p.Gln264= (c.792G>A) pathogenic?

MSH2 p.Gln264= (c.792G>A) is classified Uncertain significance in MSH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-30). Very rare (popmax 8.59e-05%, nfe); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH2 p.Gln264= (c.792G>A) in the general population?

MSH2 p.Gln264= (c.792G>A) is very rare (popmax 8.59e-05%, nfe) (gnomAD).

MSH2 p.Gln264=

Q: What condition is associated with MSH2 p.Gln264= (c.792G>A)?

MSH2 p.Gln264= (c.792G>A) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

c.792G>A · rs587779183 · VCV237409

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.59e-05%, nfe)

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.55	donor gain · deltas
Pangolin	Δ0.54	loss · gain 0.35 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 0.8, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.59e-05% European (non-Finnish) · 1/1,163,620 alleles

Overall 6.27e-05% 1/1,593,994 alleles · very rare exomes 1/1,442,210 · genomes 0/151,784 · 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.Gln264=
Coding: c.792G>A
MANE Select: NM_000251
dbSNP: rs587779183
Type: single nucleotide variant
Location: chr2:47412560 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 264: 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: hereditary neoplastic syndrome

Similar variants

MSH2 p.Gln264Ter Pathogenic ★★ same residue
MSH2 p.Gln264Pro Uncertain significance ★★ ⚠ same residue
MSH2 p.Gln264Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Gln264Leu Uncertain significance ★ ⚠ same residue
MSH2 p.Gln264fs Pathogenic ★ same residue
MSH2 p.Gln264His 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-gln264 (accessed [today's date]).

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