MSH2 p.Pro349=
c.1047T>C · rs2104251928 · VCV1608312
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
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 -0.54 | GERP -2.1, phastCons 0.058 |
| Overall | ||
| CADD | 6.08 | 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.Pro349=
- Coding
- c.1047T>C
- MANE Select
- NM_000251
- dbSNP
- rs2104251928
- Type
- single nucleotide variant
- Location
- chr2:47416400 (GRCh38)
- Gene constraint
- LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 30 PDB
- Residue 349
- a UniProt-annotated variant site (in lynch1)
Similar variants
- MSH2 p.Pro349Thr Likely pathogenic ★★ same residue
- MSH2 p.Pro349Leu Pathogenic ★★★ same residue
- MSH2 p.Pro349Ser Likely pathogenic ★★ same residue
- MSH2 p.Pro349His Likely pathogenic ★ same residue
- MSH2 p.Pro349Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- MSH2 p.Pro349Arg Likely pathogenic ★★★ same residue
- MSH2 c.1276+2T>C Pathogenic/Likely pathogenic ★★ same condition
- MSH2 c.1277-1G>T 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-pro349 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown