Is CDKL5 p.Ser796= (c.2388C>T) pathogenic?

CDKL5 p.Ser796= (c.2388C>T) is classified Likely benign in CDKL5 (ClinVar, Expert panel, 4 submitters; last evaluated 2023-04-14). Very rare (popmax 0.0044%, amr); Associated with CDKL5 disorder.

What condition is associated with CDKL5 p.Ser796= (c.2388C>T)?

CDKL5 p.Ser796= (c.2388C>T) is associated with CDKL5 disorder, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Ser796= (c.2388C>T) in the general population?

CDKL5 p.Ser796= (c.2388C>T) is very rare (popmax 0.0044%, amr) (gnomAD).

CDKL5 p.Ser796=

c.2388C>T · rs727503847 · VCV166821

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0044%, amr)

Conditions

CDKL5 disorder

ClinGen expert panel — Rett and Angelman-like Disorders VCEP

Likely Benign for CDKL5 disorder. Applied ACMG criteria (verbatim):

BS2 BP5

Curation rationale (ClinGen, verbatim)

The p.Ser796= variant is observed in at least 2 unaffected individuals (GeneDx internal database) (BS2). The p.Ser796= variant is found in a patient with an alternate molecular basis of disease (GeneDx internal database)(BP5). In summary, the p.Ser796= variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP5).

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.56	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.17	GERP -5, phastCons 0.99
Overall
CADD	14.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% Admixed American · 2/45,405 alleles

Filtering AF 0.00073% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000273%

Overall 0.000498% 6/1,204,977 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0044%	22,703
European (non-Finnish)	0.000448%	223,212

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.Ser796=
Coding: c.2388C>T
MANE Select: NM_001323289
dbSNP: rs727503847
Type: single nucleotide variant
Location: chrX:18625139 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 796: the 'disordered' region; a UniProt-annotated variant site (in dee2)

Full CDKL5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CDKL5 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.Ser796Cys Uncertain significance ★★ ⚠ 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
CDKL5 p.Arg948Ter 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-ser796 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown