Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 12 submitters
gnomAD v4.1
Common
common (popmax 81.9%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
autosomal recessive nonsyndromic hearing loss 8
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 · C>A here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.87 | GERP -3.3, phastCons 0.003 |
| Overall | ||
| CADD | 0.188 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
81.9%
African / African-American · 61,382/74,954 alleles
Filtering AF
81.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 81.1%
Overall
37.3%
601,086/1,612,724 alleles · common
exomes 528,370/1,460,650 · genomes 72,716/152,074 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 81.9% | 1 |
| Middle Eastern | 41.4% | 2 |
| Remaining individualsnot grpmax-eligible | 39% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 37.2% | 3 |
| European (non-Finnish) | 35.9% | 3 |
| Admixed American | 33.7% | 3 |
| South Asian | 29.9% | 3 |
| Amishnot grpmax-eligible | 29.5% | 3 |
| Finnishnot grpmax-eligible | 28.4% | 4 |
| East Asian | 27.5% | 4 |
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.Val151=
- Coding
- c.453G>A
- MANE Select
- NM_001256317
- dbSNP
- rs2839501
- Type
- single nucleotide variant
- Location
- chr21:42385528 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.09
- Residue 151
- the srcr domain
Similar variants
- TMPRSS3 c.1049-4G>A Likely pathogenic ★★ same condition
- TMPRSS3 c.206-2A>G Likely pathogenic ★★ same condition
- TMPRSS3 c.323-6G>A Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 c.446+1G>T Likely pathogenic ★★ same condition
- TMPRSS3 c.573-1G>A Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala138Glu Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala306Thr Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS3 p.Ala306Val Likely pathogenic ★★ same condition
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-val151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown