Is CDKL5 p.Arg444fs (c.1330_1342del) pathogenic?

CDKL5 p.Arg444fs (c.13301342del) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Arg444fs (c.1330_1342del)?

CDKL5 p.Arg444fs (c.1330_1342del) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg444fs (c.1330_1342del) in the general population?

CDKL5 p.Arg444fs (c.1330_1342del) is absent from gnomAD (gnomAD).

How is CDKL5-deficiency disorder inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDKL5 p.Arg444fs

c.1330_1342del · rs2518874193 · VCV2953180

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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 0.23	GERP -0.27, phastCons 0.97

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

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.Arg444fs
Coding: c.1330_1342del
MANE Select: NM_001323289
dbSNP: rs2518874193
Type: Deletion
Location: chrX:18604254 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 444: the 'disordered' region; a UniProt-annotated variant site (in)

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

Disease context

developmental and epileptic encephalopathy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CDKL5-deficiency disorder (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

CDKL5 p.Arg444= Benign/Likely benign ★★ same residue
CDKL5 p.Arg444Cys Benign/Likely benign ★★ ⚠ same residue
CDKL5 p.Arg444His Benign ★ ⚠ same residue
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

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-arg444fs (accessed [today's date]).

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