MSH3 p.Pro96=
c.288T>C · rs2112801662 · VCV1606725
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.1 | GERP -1.1, phastCons 0.001 |
| Overall | ||
| CADD | 10.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,028 alleles
Overall
6.2e-05%
1/1,614,192 alleles · very rare
exomes 1/1,461,852 · genomes 0/152,340 · 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
- MSH3
- Protein
- p.Pro96=
- Coding
- c.288T>C
- MANE Select
- NM_002439
- dbSNP
- rs2112801662
- Type
- single nucleotide variant
- Location
- chr5:80656461 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48 · 25 PDB
- Residue 96
- the 'disordered' region; the 'interaction with exo1' region
Similar variants
- MSH3 p.Pro96Leu Uncertain significance ★★ ⚠ same residue
- MSH3 p.Pro96Ala Uncertain significance ★ ⚠ same residue
- MSH3 p.Pro96Arg Uncertain significance ★ ⚠ same residue
- MSH3 c.1341-2A>C Likely pathogenic ★★ same type
- MSH3 c.1341-2A>G Likely pathogenic ★★ same type
- MSH3 c.1568+1G>A Likely pathogenic ★★ same type
- MSH3 c.1568+1G>C Likely pathogenic ★★ same type
- MSH3 c.1653+1G>A Likely pathogenic ★★ same type
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/msh3-p-pro96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown