TMPRSS2 p.Ser261=
c.783C>T · VCV3971066
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.211%, mid)
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 -4.8 | GERP -3.7 |
| Overall | ||
| CADD | 1.764 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.211%
Middle Eastern · 12/5,690 alleles
Filtering AF
0.122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0954%
Overall
0.00484%
78/1,610,160 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.211% | 474 |
| Admixed American | 0.0117% | 8,542 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,581 |
| European (non-Finnish) | 0.0045% | 22,246 |
| African / African-American | 0.00133% | 75,010 |
| South Asian | 0.0011% | 90,540 |
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
- TMPRSS2
- Protein
- p.Ser261=
- Coding
- c.783C>T
- MANE Select
- NM_005656
- Type
- single nucleotide variant
- Location
- chr21:41473441 (GRCh38)
- Gene constraint
- LOEUF 0.991 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.72 · 34 PDB
- Residue 261
- a disulfide bond; the peptidase s1 domain; an α-helix
Similar variants
- TMPRSS2 p.Ala216= Benign ★★ same type
- TMPRSS2 p.Tyr180= Benign ★★ same type
- TMPRSS2 p.Val160Met Benign ★★ same type
- TMPRSS2 p.Ala490Gly Uncertain significance ★ ⚠ same type
- TMPRSS2 p.Arg470Gly Uncertain significance ★ ⚠ same type
- TMPRSS2 p.Asn249Asp Uncertain significance ★ ⚠ same type
- TMPRSS2 p.Cys244Phe Uncertain significance ★ ⚠ same type
- TMPRSS2 p.Glu260Lys 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/tmprss2-p-ser261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown