CDKL5 p.Thr928=
c.2784G>A · rs369383134 · VCV516455
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0105%, sas)
Conditions
2
Angelman syndrome-like
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 2 | GERP -1.4, phastCons 0.98 |
| Overall | ||
| CADD | 1.041 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0105%
South Asian · 6/57,003 alleles
Filtering AF
0.0054%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0049%
Overall
0.00619%
68/1,098,163 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0105% | 9,500 |
| European (non-Finnish) | 0.00681% | 14,681 |
| African / African-American | 0.00173% | 57,827 |
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
- CDKL5
- Protein
- p.Thr928=
- Coding
- c.2784G>A
- MANE Select
- NM_001323289 · reported on NM_003159
- dbSNP
- rs369383134
- Type
- single nucleotide variant
- Location
- chrX:18646077 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 928
- the 'disordered' region; a UniProt-annotated variant site (in dee2); a UniProt-annotated variant site (found in a patient with infatile spasms; likely pathogenic)
Similar variants
- CDKL5 p.Thr928Met Likely benign ★★★ same residue
- CDKL5 p.Glu928Gln Uncertain significance ★ ⚠ same residue
- CDKL5 c.146-1G>A Pathogenic ★★★ same condition
- CDKL5 p.Ala157Pro Likely pathogenic ★★★ same condition
- CDKL5 p.Ala157Val Likely pathogenic ★★★ same condition
- CDKL5 p.Ala40Val Pathogenic ★★★ same condition
- CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
- CDKL5 p.Arg717= Likely pathogenic ★★★ same condition
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/cdkl5-p-thr928 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown