CDKL5 p.His339fs
c.1016del · VCV4532795
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
developmental and epileptic encephalopathy, 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CDKL5
- Protein
- p.His339fs
- Coding
- c.1016del
- MANE Select
- NM_001323289
- Type
- Deletion
- Location
- chrX:18603940 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 339
- the 'disordered' region
Disease context
developmental and epileptic encephalopathy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor CDKL5-deficiency disorder (Orphanet):
- Inheritance
- X-linked dominant
- Onset
- Infancy, Neonatal
Similar variants
- CDKL5 p.His124fs Pathogenic ★★★ same condition
- CDKL5 p.Tyr941fs Pathogenic ★★★ same condition
- CDKL5 p.Lys432_Tyr433delinsAsn Uncertain significance ★★★ same condition
- CDKL5 p.Ala486_Lys487del Benign ★★★ same condition
- CDKL5 p.Arg781fs Pathogenic ★★ same condition
- CDKL5 p.Arg943fs Likely pathogenic ★★ same condition
- CDKL5 p.Gln891fs Pathogenic ★★ same condition
- CDKL5 p.Glu55fs Pathogenic/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-his339fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown