MST1 p.Arg73His
c.218G>A · rs373890576 · VCV3212532
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.049%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.2 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -4.8 |
| Overall | ||
| CADD | 13.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.049%
East Asian · 22/44,888 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0279%
Overall
0.00632%
102/1,613,584 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.049% | 2,040 |
| Remaining individualsnot grpmax-eligible | 0.048% | 2,083 |
| South Asian | 0.0285% | 3,503 |
| African / African-American | 0.00933% | 10,721 |
| Finnishnot grpmax-eligible | 0.00157% | 63,654 |
| European (non-Finnish) | 0.00136% | 73,741 |
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.Arg73His
- Coding
- c.218G>A
- MANE Select
- NM_006282 · reported on NM_020998
- dbSNP
- rs373890576
- Type
- single nucleotide variant
- Location
- chr3:49687774 (GRCh38)
- Structure
- AlphaFold pLDDT 76.45 · 16 PDB
- Residue 73
- the protein kinase domain; an α-helix
Similar variants
- MST1 p.Arg73Cys Uncertain significance ★ same residue
- STK4 p.Glu73Gly 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-arg73his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown