TMPRSS9 p.Ala682=
c.2046G>A · rs61749983 · VCV777361
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.43%, afr)
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 -7 | GERP -3.2 |
| Overall | ||
| CADD | 0.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.43%
African / African-American · 1,818/74,962 alleles
Filtering AF
2.33%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.29%
Overall
0.13%
2,094/1,611,760 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.43% | 41 |
| Remaining individualsnot grpmax-eligible | 0.202% | 496 |
| Admixed American | 0.153% | 654 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00331% | 30,246 |
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
- TMPRSS9
- Protein
- p.Ala682=
- Coding
- c.2046G>A
- MANE Select
- NM_001395513
- dbSNP
- rs61749983
- Type
- single nucleotide variant
- Location
- chr19:2418030 (GRCh38)
- Gene constraint
- LOEUF 1.326 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.96
- Residue 682
- a disulfide bond; the peptidase s1 2 domain
Similar variants
- TMPRSS9 p.Arg433Trp Uncertain significance ★★ ⚠ same type
- TMPRSS9 p.Asp324Asn Uncertain significance ★★ ⚠ same type
- TMPRSS9 p.Pro752Leu Uncertain significance ★★ ⚠ same type
- TMPRSS9 p.Ser780Leu Uncertain significance ★★ ⚠ same type
- TMPRSS9 p.Ala449Thr Benign ★★ same type
- TMPRSS9 p.Gly832Arg Benign/Likely benign ★★ same type
- TMPRSS9 p.Ile968Val Benign ★★ same type
- TMPRSS9 p.Ser399Ter Likely pathogenic ★ 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/tmprss9-p-ala682 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown