MST1 p.Arg133Trp
c.397C>T · VCV4553601
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.63 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 25.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,078 alleles
Filtering AF
0.000292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000744%
12/1,613,244 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,078 |
| East Asian | 0.00223% | 44,890 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
| African / African-American | 0.00133% | 74,940 |
| European (non-Finnish) | 0.000678% | 147,484 |
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
- MST1
- Protein
- p.Arg133Trp
- Coding
- c.397C>T
- MANE Select
- NM_006282 · reported on NM_020998
- Type
- single nucleotide variant
- Location
- chr3:49687437 (GRCh38)
- Structure
- AlphaFold pLDDT 76.45 · 16 PDB
- Residue 133
- the protein kinase domain; an α-helix
Similar variants
- STK4 p.Thr133Ala Uncertain significance ★★ ⚠ same residue
- MST1 p.Arg133Gln Uncertain significance ★ same residue
- STK4 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
- STK4 p.Arg117Ter Pathogenic ★★ same type
- STK4 p.Arg148Ter Pathogenic ★★ same type
- STK4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same type
- STK4 p.Ala391Val Uncertain significance ★★ ⚠ same type
- STK4 p.Ala479Ser Uncertain significance ★★ ⚠ 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/mst1-p-arg133trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown