TRAK1 p.Pro708=
c.2124G>A · VCV4749559
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00668%, 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 -7.3 | GERP -3 |
| Overall | ||
| CADD | 0.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
African / African-American · 5/74,876 alleles
Filtering AF
0.00394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00361%
Overall
0.00421%
68/1,613,864 alleles · very rare
exomes 58/1,461,832 · genomes 10/152,032 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00668% | 14,975 |
| European (non-Finnish) | 0.005% | 20,000 |
| East Asian | 0.00223% | 44,866 |
| South Asian | 0.0022% | 45,539 |
| Admixed American | 0.00167% | 59,990 |
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.Pro708=
- Coding
- c.2124G>A
- MANE Select
- NM_001042646
- Type
- single nucleotide variant
- Location
- chr3:42222999 (GRCh38)
- Gene constraint
- LOEUF 0.461 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 59.19
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-pro708 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown