GAK p.Pro586=
c.1758G>A · rs35964990 · VCV778134
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.21%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -14 | GERP -3.4 |
| Overall | ||
| CADD | 0.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.21%
African / African-American · 4,657/74,982 alleles
Filtering AF
6.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6%
Overall
0.353%
5,702/1,613,362 alleles · common
exomes 2,967/1,461,162 · genomes 2,735/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.21% | 16 |
| Remaining individualsnot grpmax-eligible | 0.517% | 193 |
| Admixed American | 0.511% | 196 |
| Middle Eastern | 0.445% | 225 |
| Ashkenazi Jewishnot grpmax-eligible | 0.331% | 302 |
| South Asian | 0.0275% | 3,642 |
| European (non-Finnish) | 0.022% | 4,538 |
| Finnishnot grpmax-eligible | 0.00944% | 10,595 |
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
- GAK
- Protein
- p.Pro586=
- Coding
- c.1758G>A
- MANE Select
- NM_005255
- dbSNP
- rs35964990
- Type
- single nucleotide variant
- Location
- chr4:877713 (GRCh38)
- Gene constraint
- LOEUF 0.687 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.32 · 7 PDB
- Residue 586
- the c2 tensin-type domain
Similar variants
- GAK p.Ala1255= Likely benign ★★ same type
- GAK p.Asp1297= Benign ★★ same type
- GAK p.Glu1020= Benign/Likely benign ★★ same type
- GAK p.Glu816Lys Benign ★★ same type
- GAK p.His1287= Benign ★★ same type
- GAK p.Lys1265Arg Benign ★★ same type
- GAK p.Pro1139Arg Benign ★★ ⚠ same type
- GAK p.Pro720Ser Benign/Likely benign ★★ 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/gak-p-pro586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown