TMPRSS15 p.Ser545=
c.1635C>T · rs558352557 · VCV2869044
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.99 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP -0.97, phastCons 1 |
| Overall | ||
| CADD | 4.939 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,084 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.00118%
19/1,614,030 alleles · ultra-rare
exomes 16/1,461,730 · genomes 3/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,060 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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.Ser545=
- Coding
- c.1635C>T
- MANE Select
- NM_002772
- dbSNP
- rs558352557
- Type
- single nucleotide variant
- Location
- chr21:18332103 (GRCh38)
- Gene constraint
- LOEUF 1.12 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.03 · 14 PDB
- Residue 545
- the cub 2 domain; a UniProt-annotated variant site (in); an α-helix
Similar variants
- TMPRSS15 p.Ser545Cys Benign ★ same residue
- 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
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-ser545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown