CDKL5 p.Ser438fs
c.1311dup · rs267608623 · VCV143774
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Pathogenic for CDKL5 disorder. Applied ACMG criteria (verbatim):
PM6 PVS1 PM2_Supporting
Curation rationale (ClinGen, verbatim)
The c.1311dup variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The c.1311dup variant in CDKL5 has been reported as a de novo occurrence (biological parentage unconfirmed) in an individual with early onset seizures and infantile spasms (PMID 19793311) (PM6). The c.1311dup variant in CDKL5 is absent from gnomAD v2.1.1 (PM2_supporting). In summary, the c.1311dup variant in CDKL5 is classified as pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PVS1, PM6, PM2_supporting).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
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 3.8 | GERP -0.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- CDKL5
- Protein
- p.Ser438fs
- Coding
- c.1311dup
- MANE Select
- NM_001323289
- dbSNP
- rs267608623
- Type
- Duplication
- Location
- chrX:18604234 (GRCh38)
- Structure
- AlphaFold pLDDT 53.76 · 3 PDB
- Residue 438
- the 'disordered' region
Similar variants
- CDKL5 c.65dupG Pathogenic/Likely pathogenic ★★ same condition
- CDKL5 p.Ala166fs Pathogenic ★★ same condition
- CDKL5 p.Arg558fs Pathogenic/Likely pathogenic ★★ same condition
- CDKL5 p.Leu184fs Pathogenic ★★ same condition
- CDKL5 p.Thr792fs Pathogenic/Likely pathogenic ★★ same condition
- CDKL5 p.Ala122fs Pathogenic ★ same condition
- CDKL5 p.Ala362fs Pathogenic ★ same condition
- CDKL5 p.Gln290fs 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-ser438fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown