TMPRSS3 p.Glu104=
c.312G>A · rs747805672 · VCV2075163
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0533%, amr)
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 -0.054 | GERP -2.3, phastCons 0.55 |
| Overall | ||
| CADD | 4.296 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0533%
Admixed American · 32/60,012 alleles
Filtering AF
0.0387%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.00204%
33/1,613,852 alleles · ultra-rare
exomes 31/1,461,614 · genomes 2/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0533% | 1,875 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
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.Glu104=
- Coding
- c.312G>A
- MANE Select
- NM_001256317
- dbSNP
- rs747805672
- Type
- single nucleotide variant
- Location
- chr21:42388939 (GRCh38)
- Gene constraint
- LOEUF 1.106 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 87.09
- Residue 104
- the ldl-receptor class a domain
Similar variants
- TMPRSS3 p.Glu104Lys Pathogenic/Likely pathogenic ★★ same residue
- TMPRSS3 p.Glu104Gly Likely pathogenic ★ 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
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-glu104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown