Is MSH2 p.Ile511= (c.1533T>A) pathogenic?

MSH2 p.Ile511= (c.1533T>A) is classified Likely benign in MSH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-22). Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH2 p.Ile511= (c.1533T>A) in the general population?

MSH2 p.Ile511= (c.1533T>A) is absent from gnomAD v4.1 (gnomAD).

MSH2 p.Ile511=

Q: What condition is associated with MSH2 p.Ile511= (c.1533T>A)?

MSH2 p.Ile511= (c.1533T>A) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

c.1533T>A · rs1553366529 · VCV2020817

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.4	GERP -1.7, phastCons 1
Overall
CADD	7.922	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.Ile511=
Coding: c.1533T>A
MANE Select: NM_000251
dbSNP: rs1553366529
Type: single nucleotide variant
Location: chr2:47466680 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 511: a β-strand

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.Ile511Met Uncertain significance ★★ ⚠ same residue
MSH2 p.Ile511Phe Uncertain significance ★ ⚠ same residue
MSH2 p.Ile511Ser Uncertain significance ★ ⚠ same residue
MSH2 p.Ile511Thr Likely benign ★ same residue
MSH2 p.Ile511fs 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-ile511 (accessed [today's date]).

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