Is MSH2 p.Ile511fs (c.1532_1538del) pathogenic?

MSH2 p.Ile511fs (c.15321538del) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-13). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH2 p.Ile511fs (c.1532_1538del)?

MSH2 p.Ile511fs (c.1532_1538del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Ile511fs (c.1532_1538del) in the general population?

MSH2 p.Ile511fs (c.1532_1538del) is no gnomAD frequency available for this variant (gnomAD).

MSH2 p.Ile511fs

c.1532_1538del · rs2528748953 · VCV1774646

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MSH2
Protein: p.Ile511fs
Coding: c.1532_1538del
MANE Select: NM_000251
dbSNP: rs2528748953
Type: Deletion
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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSH2 p.Ile511Met Uncertain significance ★★ ⚠ same residue
MSH2 p.Ile511= Likely benign ★★ same residue
MSH2 p.Ile511Phe Uncertain significance ★ ⚠ same residue
MSH2 p.Ile511Thr Likely benign ★ same residue
MSH2 c.646-3_654del Likely pathogenic ★★★ same condition
MSH2 p.Arg638fs Pathogenic ★★★ same condition
MSH2 p.Asn139fs Pathogenic ★★★ same condition
MSH2 p.Asn263fs 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-ile511fs (accessed [today's date]).

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