Is MSH2 p.Ala600= (c.1800T>G) pathogenic?

MSH2 p.Ala600= (c.1800T>G) is classified Likely benign in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH2 p.Ala600= (c.1800T>G)?

MSH2 p.Ala600= (c.1800T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Ala600= (c.1800T>G) in the general population?

MSH2 p.Ala600= (c.1800T>G) is absent from gnomAD v4.1 (gnomAD).

MSH2 p.Ala600=

c.1800T>G · rs1667233707 · VCV1780401

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -3.6, phastCons 1
Overall
CADD	6.775	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSH2
Protein: p.Ala600=
Coding: c.1800T>G
MANE Select: NM_000251
dbSNP: rs1667233707
Type: single nucleotide variant
Location: chr2:47475065 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 600: an α-helix; a UniProt-annotated variant site (in lynch1)

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSH2 p.Ala600Val Likely pathogenic ★★ same residue
MSH2 p.Ala600Asp Likely pathogenic ★ same residue
MSH2 p.Ala600Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ala600Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ala600fs Pathogenic ★ same residue
MSH2 p.Ala600Pro Uncertain significance ★ ⚠ same residue
MSH2 p.Ala600Thr Likely benign ★ same residue
MSH2 c.1076+1G>A 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-ala600 (accessed [today's date]).

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