TMPRSS15 p.Pro898=
c.2694G>A · rs759593084 · VCV1941449
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0119%, amr)
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 -0.46 | GERP -4.2, phastCons 0.14 |
| Overall | ||
| CADD | 6.261 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0119%
Admixed American · 7/59,038 alleles
Filtering AF
0.00551%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00386%
Overall
0.00182%
29/1,591,466 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0119% | 8,434 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00688% | 14,529 |
| East Asian | 0.00676% | 14,796 |
| Remaining individualsnot grpmax-eligible | 0.0065% | 15,393 |
| Finnishnot grpmax-eligible | 0.00322% | 31,038 |
| African / African-American | 0.00137% | 73,028 |
| South Asian | 0.00111% | 89,934 |
| European (non-Finnish) | 0.000772% | 129,494 |
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
- TMPRSS15
- Protein
- p.Pro898=
- Coding
- c.2694G>A
- MANE Select
- NM_002772
- dbSNP
- rs759593084
- Type
- single nucleotide variant
- Location
- chr21:18279034 (GRCh38)
- Gene constraint
- LOEUF 1.12 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.03 · 14 PDB
- Residue 898
- the peptidase s1 domain; an α-helix
Similar variants
- TMPRSS15 c.1922-1G>A Likely pathogenic ★★ same type
- TMPRSS15 c.2033-1G>A Likely pathogenic ★★ same type
- TMPRSS15 c.2486+1G>A Likely pathogenic ★★ same type
- TMPRSS15 p.Arg871Ter Pathogenic/Likely pathogenic ★★ same type
- TMPRSS15 p.Ser712Ter Pathogenic ★★ same type
- TMPRSS15 p.Ala491Thr Uncertain significance ★★ ⚠ same type
- TMPRSS15 p.Ala744Val Uncertain significance ★★ ⚠ same type
- TMPRSS15 p.Arg1000His 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/tmprss15-p-pro898 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown