MSH2 p.Arg55=
c.163C>A · rs587782354 · VCV1003525
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
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 3.9 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 16.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,178,764 alleles
Overall
6.22e-05%
1/1,608,268 alleles · very rare
exomes 1/1,455,912 · genomes 0/152,356 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MSH2
- Protein
- p.Arg55=
- Coding
- c.163C>A
- MANE Select
- NM_000251
- dbSNP
- rs587782354
- Type
- single nucleotide variant
- Location
- chr2:47403354 (GRCh38)
- Gene constraint
- LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.60 · 30 PDB
- Residue 55
- an α-helix; a UniProt-annotated variant site (decreases protein levels)
Similar variants
- MSH2 p.Arg55Pro Uncertain significance ★★ ⚠ same residue
- MSH2 p.Arg55Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- MSH2 p.Arg55Gln Likely benign ★★★ same residue
- MSH2 p.Arg55Trp Uncertain significance ★★ ⚠ same residue
- MSH2 p.Arg55Leu Uncertain significance ★ ⚠ 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
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-arg55 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown