TEK p.Ala46=
c.138C>T · rs76223779 · VCV366391
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.51%, afr)
Conditions
1
multiple cutaneous and mucosal venous malformations
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 -0.72 | GERP -1.9, phastCons 0.007 |
| Overall | ||
| CADD | 9.352 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.51%
African / African-American · 1,886/74,996 alleles
Filtering AF
2.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.38%
Overall
0.129%
2,076/1,614,062 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.51% | 40 |
| Remaining individualsnot grpmax-eligible | 0.136% | 735 |
| Admixed American | 0.13% | 769 |
| Middle Eastern | 0.066% | 1,516 |
| East Asian | 0.0134% | 7,480 |
| South Asian | 0.00439% | 22,763 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- TEK
- Protein
- p.Ala46=
- Coding
- c.138C>T
- MANE Select
- NM_000459
- dbSNP
- rs76223779
- Type
- single nucleotide variant
- Location
- chr9:27157916 (GRCh38)
- Gene constraint
- LOEUF 0.368 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 17 PDB
- Residue 46
- a disulfide bond; a UniProt-annotated variant site (in glc3e; formation of protein aggregates); the ig-like c2-type 1 domain; a β-strand
Similar variants
- TEK p.Ala46Val Uncertain significance ★ ⚠ same residue
- TEK p.Arg1099Ter Pathogenic ★★ same condition
- TEK p.Arg849Trp Pathogenic ★★ ⚠ same condition
- TEK p.Arg915Cys Pathogenic/Likely pathogenic ★★ same condition
- TEK p.Arg915His Pathogenic/Likely pathogenic ★★ same condition
- TEK p.Arg918Cys Pathogenic/Likely pathogenic ★★ same condition
- TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same condition
- TEK p.Tyr897Asn Pathogenic/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/tek-p-ala46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown