Is MSH2 p.Asp487= (c.1461C>T) pathogenic?

MSH2 p.Asp487= (c.1461C>T) is classified Benign/Likely benign in MSH2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-09). Absent from gnomAD v4.1; Associated with Lynch syndrome 1.

What condition is associated with MSH2 p.Asp487= (c.1461C>T)?

MSH2 p.Asp487= (c.1461C>T) is associated with Lynch syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Asp487= (c.1461C>T) in the general population?

MSH2 p.Asp487= (c.1461C>T) is absent from gnomAD v4.1 (gnomAD).

How is Lynch syndrome inherited?

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

MSH2 p.Asp487=

c.1461C>T · rs35107951 · VCV762563

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Lynch syndrome 1

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 -0.9	GERP -1.5, phastCons 0.002
Overall
CADD	5.535	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.Asp487=
Coding: c.1461C>T
MANE Select: NM_000251
dbSNP: rs35107951
Type: single nucleotide variant
Location: chr2:47463105 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 487: an α-helix; a UniProt-annotated variant site (decreased mismatch repair activity)

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

Disease context

Lynch syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH2 p.Asp487Ala Uncertain significance ★ ⚠ same residue
MSH2 p.Asp487Asn Uncertain significance ★ ⚠ same residue
MSH2 p.Asp487Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Asp487Gly Likely benign ★ same residue
MSH2 p.Asp487delinsGluTer Pathogenic ★★ 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

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-asp487 (accessed [today's date]).

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