TMPRSS6 p.Pro387=
c.1161G>A · rs112333860 · VCV3042671
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.232%, afr)
Conditions
1
TMPRSS6-related disorder
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 -20 | GERP -2.5 |
| Overall | ||
| CADD | 0.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.232%
African / African-American · 174/74,994 alleles
Filtering AF
0.204%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.193%
Overall
0.0159%
256/1,613,672 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.232% | 431 |
| Admixed American | 0.0417% | 2,399 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,807 |
| Middle Eastern | 0.0165% | 6,060 |
| European (non-Finnish) | 0.00331% | 30,252 |
| South Asian | 0.0033% | 30,317 |
| East Asian | 0.00223% | 44,842 |
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.Pro387=
- Coding
- c.1161G>A
- MANE Select
- NM_001374504
- dbSNP
- rs112333860
- Type
- single nucleotide variant
- Location
- chr22:37084330 (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 387
- the cub 2 domain
Disease context
TMPRSS6-related disorder
Similar variants
- TMPRSS6 p.Pro387Leu Uncertain significance ★★ ⚠ same residue
- TMPRSS6 p.Arg590Ter Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS6 p.Lys70Ter Likely pathogenic ★★ same condition
- TMPRSS6 p.Ser552Ter Pathogenic ★★ same condition
- TMPRSS6 p.Tyr346Ter Likely pathogenic ★★ same condition
- TMPRSS6 c.2114-1G>A Likely pathogenic ★ same condition
- TMPRSS6 p.Arg262Ter Likely pathogenic ★ same condition
- TMPRSS6 p.Trp303Ter 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/tmprss6-p-pro387 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown