CDKL5 p.Arg305=
c.915T>C · rs1170498240 · VCV1025252
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000336%, nfe)
Conditions
2
CDKL5 disorder
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 -0.78 | GERP -4.4, phastCons 0.002 |
| Overall | ||
| CADD | 3.962 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000336%
European (non-Finnish) · 3/893,204 alleles
Filtering AF
8.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000248%
3/1,207,948 alleles · very rare
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.Arg305=
- Coding
- c.915T>C
- MANE Select
- NM_001323289
- dbSNP
- rs1170498240
- Type
- single nucleotide variant
- Location
- chrX:18598551 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 305
- the 'disordered' region
Similar variants
- CDKL5 p.Arg305His Likely benign ★★★ ⚠ same residue
- CDKL5 p.Arg305Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg305 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown