PHKA2 p.Leu445=
c.1333T>C · rs200298889 · VCV747950
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 7.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,350 alleles
Filtering AF
0.00454%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00306%
Overall
0.00091%
11/1,208,526 alleles · ultra-rare
exomes 10/1,095,907 · genomes 1/112,619 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.023% | 4,350 |
| African / African-American | 0.0104% | 9,573 |
| Remaining individualsnot grpmax-eligible | 0.0042% | 23,784 |
| European (non-Finnish) | 0.000224% | 446,692 |
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.Leu445=
- Coding
- c.1333T>C
- MANE Select
- NM_000292
- dbSNP
- rs200298889
- Type
- single nucleotide variant
- Location
- chrX:18926579 (GRCh38)
- Structure
- AlphaFold pLDDT 81.36
Similar variants
- PHKA2 p.Leu445fs Likely pathogenic ★ 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
- PHKA2 p.Arg186His 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-leu445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown