CDKL5 p.Ile72=
c.216T>A · rs267608439 · VCV143798
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00217%, amr)
Conditions
1
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 -0.58 | GERP -4.8, phastCons 0.038 |
| Overall | ||
| CADD | 6.026 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00217%
Admixed American · 1/46,007 alleles
Filtering AF
8.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000331%
4/1,209,127 alleles · very rare
exomes 4/1,095,492 · genomes 0/113,635 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00217% | 46,007 |
| European (non-Finnish) | 0.000336% | 297,733 |
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.Ile72=
- Coding
- c.216T>A
- MANE Select
- NM_001323289
- dbSNP
- rs267608439
- Type
- single nucleotide variant
- Location
- chrX:18575424 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 72
- the protein kinase domain; a UniProt-annotated variant site (in dee2)
Similar variants
- CDKL5 p.Ile72Thr Pathogenic ★★★ same residue
- CDKL5 p.Ile72Asn Likely pathogenic ★ same residue
- CDKL5 p.Ile72del Uncertain significance ★ same residue
- RS1 p.Glu72Lys Pathogenic ★★★ same residue
- RS1 p.Glu72Asp Pathogenic ★★ ⚠ same residue
- RS1 p.Glu72Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
- RS1 p.Glu72Gly Pathogenic ★★ same residue
- RS1 p.Glu72= Likely benign ★★ same residue
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-ile72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown