Is MSH2 p.Ile511Ser (c.1532T>G) pathogenic?

MSH2 p.Ile511Ser (c.1532T>G) is classified Uncertain significance in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-10). AlphaMissense: likely pathogenic (0.9776); Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Ile511Ser (c.1532T>G)?

MSH2 p.Ile511Ser (c.1532T>G) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is MSH2 p.Ile511Ser (c.1532T>G) in the general population?

MSH2 p.Ile511Ser (c.1532T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSH2 p.Ile511Ser (c.1532T>G)?

AlphaMissense predicts likely pathogenic (score 0.9776) — an in-silico prediction, not a clinical call.

MSH2 p.Ile511Ser

c.1532T>G · rs1573553170 · VCV656912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9776 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
AlphaMissense	0.9776	likely pathogenic
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -15.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 80 kb · p 4.9e-24 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ile511Ser
Coding: c.1532T>G
MANE Select: NM_000251
dbSNP: rs1573553170
Type: single nucleotide variant
Location: chr2:47466679 (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

Similar variants

MSH2 p.Ile511= Likely benign ★★ same residue
MSH2 p.Ile511Met Uncertain significance ★★ ⚠ same residue
MSH2 p.Ile511Phe Uncertain significance ★ ⚠ same residue
MSH2 p.Ile511Thr Likely benign ★ same residue
MSH2 c.1276+2T>C Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.1277-1G>T Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.1510+1G>T Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.1510+2T>C Pathogenic/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-ile511ser (accessed [today's date]).

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