MSH3 p.Ser8=
c.24G>A · rs1320023097 · VCV751405
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.5e-05%, nfe)
Conditions
1
hereditary neoplastic syndrome
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 -0.83 | GERP -3.6 |
| Overall | ||
| CADD | 4.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.5e-05%
European (non-Finnish) · 1/1,175,856 alleles
Overall
6.24e-05%
1/1,601,988 alleles · very rare
exomes 1/1,449,934 · genomes 0/152,054 · 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.Ser8=
- Coding
- c.24G>A
- MANE Select
- NM_002439
- dbSNP
- rs1320023097
- Type
- single nucleotide variant
- Location
- chr5:80654751 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48 · 25 PDB
Similar variants
- MSH3 p.Ser8Leu Uncertain significance ★★ ⚠ same residue
- MSH3 p.Ser8Pro Uncertain significance ★★ ⚠ same residue
- MSH3 c.1341-2A>C Likely pathogenic ★★ same condition
- MSH3 c.1341-2A>G Likely pathogenic ★★ same condition
- MSH3 c.1568+1G>C Likely pathogenic ★★ same condition
- MSH3 c.1653+1G>A Likely pathogenic ★★ same condition
- MSH3 c.1764-1G>A Pathogenic/Likely pathogenic ★★ same condition
- MSH3 c.1764-2A>C 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/msh3-p-ser8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown