MSH3 p.Gly319=
c.957A>C · rs2546722883 · VCV1767427
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
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 -0.13 | GERP -3.5, phastCons 0.031 |
| Overall | ||
| CADD | 6.006 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,084 alleles
Overall
6.84e-05%
1/1,461,810 alleles · very rare
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.Gly319=
- Coding
- c.957A>C
- MANE Select
- NM_002439
- dbSNP
- rs2546722883
- Type
- single nucleotide variant
- Location
- chr5:80672788 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48 · 25 PDB
- Residue 319
- a β-strand
Similar variants
- 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
- MSH3 c.1764-2A>G Pathogenic/Likely pathogenic ★★ same condition
- MSH3 c.1896+1G>A 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-gly319 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown