TMPRSS3 p.Glu347=
c.1041G>A · rs779969755 · VCV1626919
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 0.19 | GERP -3.9, phastCons 0.97 |
| Overall | ||
| CADD | 8.556 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,994 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.0013%
21/1,613,836 alleles · very rare
exomes 19/1,461,604 · genomes 2/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,994 |
| European (non-Finnish) | 0.00161% | 62,099 |
| Finnishnot grpmax-eligible | 0.00156% | 64,044 |
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.Glu347=
- Coding
- c.1041G>A
- MANE Select
- NM_001256317
- dbSNP
- rs779969755
- Type
- single nucleotide variant
- Location
- chr21:42380124 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.09
- Residue 347
- the peptidase s1 domain
Similar variants
- 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
- TMPRSS3 p.Ala306Val 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-glu347 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown