TMPRSS6 p.Pro150=
c.450C>T · rs200213417 · VCV2720817
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0825%, mid)
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 · G>T here scores Δ0.99 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.1 |
| Overall | ||
| CADD | 0.189 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0825%
Middle Eastern · 5/6,062 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0458%
Overall
0.0105%
169/1,614,170 alleles · ultra-rare
exomes 134/1,461,874 · genomes 35/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0825% | 1,212 |
| South Asian | 0.0637% | 1,570 |
| African / African-American | 0.044% | 2,274 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.00666% | 15,005 |
| European (non-Finnish) | 0.00508% | 19,667 |
| East Asian | 0.00446% | 22,441 |
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
- TMPRSS6
- Protein
- p.Pro150=
- Coding
- c.450C>T
- MANE Select
- NM_001374504
- dbSNP
- rs200213417
- Type
- single nucleotide variant
- Location
- chr22:37096045 (GRCh38)
- Gene constraint
- LOEUF 0.821 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 84.69 · 1 PDB
- Residue 150
- the sea domain; a β-strand
Similar variants
- TMPRSS6 c.1342+1G>A Pathogenic/Likely pathogenic ★★ same type
- TMPRSS6 p.Arg590Ter Pathogenic/Likely pathogenic ★★ same type
- TMPRSS6 p.Asp512Asn Likely pathogenic ★★ same type
- TMPRSS6 p.Gly433Arg Pathogenic/Likely pathogenic ★★ ⚠ same type
- TMPRSS6 p.Lys70Ter Likely pathogenic ★★ same type
- TMPRSS6 p.Ser552Ter Pathogenic ★★ same type
- TMPRSS6 p.Tyr346Ter Likely pathogenic ★★ same type
- TMPRSS6 p.Ala164Thr Uncertain significance ★★ ⚠ 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/tmprss6-p-pro150 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown