MSH3 c.237+3A>C
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 | ||
| Splice region | donor +3 | donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | Δ0.30 | donor gain · deltas |
| Pangolin | Δ0.75 | loss · gain 0.31 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -2.5, phastCons 0.9 |
| Non-coding constraint | Z -2.00 | 1 kb window · o/e 1.19 · regional · uncalibrated |
| Overall | ||
| CADD | 15.78 | 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
- Coding
- c.237+3A>C
- MANE Select
- NM_002439
- dbSNP
- rs745911924
- Type
- single nucleotide variant
- Location
- chr5:80654967 (GRCh38)
- Gene constraint
- LOEUF 1.027 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.48 · 25 PDB
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-c-237-plus-3a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown