TMPRSS6 p.Pro320=
c.960G>A · rs2543517 · VCV2056716
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.253%, afr)
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 -8.6 | GERP -2.9 |
| Overall | ||
| CADD | 0.459 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.253%
African / African-American · 190/75,008 alleles
Filtering AF
0.224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.212%
Overall
0.0163%
263/1,614,134 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.253% | 395 |
| Admixed American | 0.0367% | 2,728 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| South Asian | 0.00549% | 18,217 |
| East Asian | 0.00223% | 44,872 |
| European (non-Finnish) | 0.00203% | 49,167 |
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.Pro320=
- Coding
- c.960G>A
- MANE Select
- NM_001374504
- dbSNP
- rs2543517
- Type
- single nucleotide variant
- Location
- chr22:37086296 (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 320
- the cub 1 domain
Similar variants
- TMPRSS6 p.Pro320Thr Uncertain significance ★★ ⚠ same residue
- TMPRSS6 p.Pro320Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown