TMPRSS6 p.Ser617=
c.1851C>T · rs1926663670 · VCV902221
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00499%, eas)
Conditions
1
microcytic anemia
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 -0.32 | GERP -3.6, phastCons 0.02 |
| Overall | ||
| CADD | 2.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00499%
East Asian · 2/40,082 alleles
Filtering AF
0.000827%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000309%
Overall
0.000215%
3/1,393,880 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00499% | 20,041 |
| European (non-Finnish) | 8.84e-05% | 1,130,933 |
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.Ser617=
- Coding
- c.1851C>T
- MANE Select
- NM_001374504
- dbSNP
- rs1926663670
- Type
- single nucleotide variant
- Location
- chr22:37069335 (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 617
- the peptidase s1 domain; an active site; an α-helix; a disulfide bond
Similar variants
- TMPRSS6 p.Arg590Ter Pathogenic/Likely pathogenic ★★ same condition
- TMPRSS6 p.Asp512Asn Likely pathogenic ★★ same condition
- TMPRSS6 p.Ala700Val Uncertain significance ★★ ⚠ same condition
- TMPRSS6 p.Arg43Cys Uncertain significance ★★ ⚠ same condition
- TMPRSS6 p.Arg545Trp Uncertain significance ★★ ⚠ same condition
- TMPRSS6 p.Arg735His Uncertain significance ★★ ⚠ same condition
- TMPRSS6 p.Arg96His Uncertain significance ★★ ⚠ same condition
- TMPRSS6 p.Glu151Lys Uncertain significance ★★ ⚠ 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-ser617 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown