CDKL5 p.Ala311=
c.933A>G · rs1348754333 · VCV701541
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
Conditions
2
Angelman syndrome-like
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -4.4, phastCons 1 |
| Overall | ||
| CADD | 6.744 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,373 alleles
Filtering AF
0.00174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000882%
Overall
0.000744%
9/1,209,328 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,373 |
| Admixed American | 0.00655% | 15,260 |
| European (non-Finnish) | 0.000559% | 178,887 |
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.Ala311=
- Coding
- c.933A>G
- MANE Select
- NM_001323289
- dbSNP
- rs1348754333
- Type
- single nucleotide variant
- Location
- chrX:18598569 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 311
- the 'disordered' region
Similar variants
- 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
- CDKL5 p.Arg948Ter Pathogenic ★★★ same condition
- CDKL5 p.Asp193Gly 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-ala311 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown