TMPRSS3 p.Ile172=
c.516C>T · rs141476064 · VCV1199147
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0734%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -0.4, phastCons 1 |
| Overall | ||
| CADD | 12.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0734%
African / African-American · 55/74,888 alleles
Filtering AF
0.0579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0523%
Overall
0.00477%
77/1,614,004 alleles · ultra-rare
exomes 44/1,461,866 · genomes 33/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0734% | 1,362 |
| Middle Eastern | 0.0164% | 6,084 |
| Admixed American | 0.00833% | 12,000 |
| South Asian | 0.00439% | 22,772 |
| European (non-Finnish) | 0.00102% | 98,335 |
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
- TMPRSS3
- Protein
- p.Ile172=
- Coding
- c.516C>T
- MANE Select
- NM_001256317
- dbSNP
- rs141476064
- Type
- single nucleotide variant
- Location
- chr21:42385465 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.09
- Residue 172
- the srcr domain
Similar variants
- TMPRSS3 p.Ile172Thr Uncertain significance ★ ⚠ same residue
- TMPRSS3 c.1049-4G>A Likely pathogenic ★★ same type
- TMPRSS3 c.206-2A>G Likely pathogenic ★★ same type
- TMPRSS3 c.323-6G>A Pathogenic/Likely pathogenic ★★ same type
- TMPRSS3 c.446+1G>T Likely pathogenic ★★ same type
- TMPRSS3 c.573-1G>A Likely pathogenic ★★ same type
- TMPRSS3 p.Ala138Glu Pathogenic/Likely pathogenic ★★ same type
- TMPRSS3 p.Ala306Thr Pathogenic/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/tmprss3-p-ile172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown