PHKA2 p.Ile586=
c.1758T>C · rs146853190 · VCV255769
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.069%, mid)
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 3.5 | GERP 0.52, phastCons 1 |
| Overall | ||
| CADD | 9.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.069%
Middle Eastern · 3/4,350 alleles
Filtering AF
0.0376%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0327%
Overall
0.00299%
36/1,204,109 alleles · ultra-rare
exomes 24/1,091,559 · genomes 12/112,550 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.069% | 1,450 |
| African / African-American | 0.0524% | 1,909 |
| Remaining individualsnot grpmax-eligible | 0.00633% | 15,799 |
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
- PHKA2
- Protein
- p.Ile586=
- Coding
- c.1758T>C
- MANE Select
- NM_000292
- dbSNP
- rs146853190
- Type
- single nucleotide variant
- Location
- chrX:18924091 (GRCh38)
- Structure
- AlphaFold pLDDT 81.36
Similar variants
- PHKA2 p.Ile586Ser Uncertain significance ★ ⚠ same residue
- PHKA2 p.Ile586Val Uncertain significance ★ ⚠ same residue
- PHKA2 c.1325-2A>G Likely pathogenic ★★ same type
- PHKA2 c.2597+1G>A Pathogenic/Likely pathogenic ★★ same type
- PHKA2 c.537+2T>C Pathogenic/Likely pathogenic ★★ same type
- PHKA2 c.918+1G>A Pathogenic/Likely pathogenic ★★ same type
- PHKA2 p.Arg1111Ter Pathogenic ★★ same type
- PHKA2 p.Arg186Cys Pathogenic/Likely 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/phka2-p-ile586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown