TMPRSS6 p.Ala700=
c.2100C>T · VCV4684483
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0194%, eas)
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 1.3 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 7.441 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0194%
East Asian · 8/41,186 alleles
Filtering AF
0.00962%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.007%
Overall
0.00101%
14/1,392,596 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0194% | 5,148 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,055 |
| Admixed American | 0.00192% | 52,148 |
| European (non-Finnish) | 0.000261% | 383,361 |
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.Ala700=
- Coding
- c.2100C>T
- MANE Select
- NM_001374504
- Type
- single nucleotide variant
- Location
- chr22:37069086 (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 700
- the peptidase s1 domain
Similar variants
- TMPRSS6 p.Ala700Val Uncertain significance ★★ ⚠ same residue
- TMPRSS6 p.Ala700Gly 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-ala700 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown