MSH3 p.Val304=
c.912G>A · rs2112814232 · VCV1124796
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.74 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.38 | gain · loss 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 19.81 | 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
- MSH3
- Protein
- p.Val304=
- Coding
- c.912G>A
- MANE Select
- NM_002439
- dbSNP
- rs2112814232
- Type
- single nucleotide variant
- Location
- chr5:80672743 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48 · 25 PDB
- Residue 304
- 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-val304 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown