Is MSH2 p.Leu52Pro (c.155_156delinsCT) pathogenic?

MSH2 p.Leu52Pro (c.155156delinsCT) is classified Conflicting classifications of pathogenicity in MSH2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-08-26). No gnomAD frequency available for this variant; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Leu52Pro (c.155_156delinsCT)?

MSH2 p.Leu52Pro (c.155_156delinsCT) is associated with Hereditary nonpolyposis colorectal neoplasms, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Leu52Pro (c.155_156delinsCT) in the general population?

MSH2 p.Leu52Pro (c.155_156delinsCT) is no gnomAD frequency available for this variant (gnomAD).

MSH2 p.Leu52Pro

c.155_156delinsCT · rs2465587066 · VCV1775034

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 80 kb · p 4.9e-24 · regional, not allelic

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.Leu52Pro
Coding: c.155_156delinsCT
MANE Select: NM_000251
dbSNP: rs2465587066
Type: Indel
Location: chr2:47403346 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 52: an α-helix

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.Leu52fs Pathogenic ★★ same residue
MSH2 p.Leu52= Benign/Likely benign ★★ same residue
MSH2 p.Leu52Met Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Leu52Val Uncertain significance ★ ⚠ same residue
MSH2 p.Ala107fs Pathogenic ★★ same condition
MSH2 p.Asp156fs Pathogenic ★★ same condition
MSH2 p.Glu529fs Pathogenic ★★ same condition
MSH2 p.Glu808Ter 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-leu52pro (accessed [today's date]).

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