TRAK1 p.Ala433=
c.1299C>A · VCV3341592
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0776%, nfe)
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 0.44 | GERP 1, phastCons 0.042 |
| Overall | ||
| CADD | 5.912 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0776%
European (non-Finnish) · 916/1,180,044 alleles
Filtering AF
0.0734%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0718%
Overall
0.0595%
960/1,614,236 alleles · ultra-rare
exomes 886/1,461,894 · genomes 74/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0776% | 1,288 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,500 |
| African / African-American | 0.0133% | 7,505 |
| Admixed American | 0.01% | 10,005 |
| Finnishnot grpmax-eligible | 0.00312% | 32,021 |
| South Asian | 0.0011% | 91,084 |
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
- TRAK1
- Protein
- p.Ala433=
- Coding
- c.1299C>A
- MANE Select
- NM_001042646
- Type
- single nucleotide variant
- Location
- chr3:42200926 (GRCh38)
- Gene constraint
- LOEUF 0.461 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.19
- Residue 433
- the 'interaction with hgs' region
Similar variants
- TRAK1 c.1963+258C>T Uncertain significance ★★ same type
- TRAK1 p.Ala334Thr Uncertain significance ★★ ⚠ same type
- TRAK1 p.Ala498Val Uncertain significance ★★ ⚠ same type
- TRAK1 p.Ala655Val Uncertain significance ★★ ⚠ same type
- TRAK1 p.Ala861Thr Uncertain significance ★★ ⚠ same type
- TRAK1 p.Arg117Gln Uncertain significance ★★ ⚠ same type
- TRAK1 p.Arg165Gln Uncertain significance ★★ ⚠ same type
- TRAK1 p.Arg279Cys Uncertain significance ★★ 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/trak1-p-ala433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown