Is CDKL5 p.Thr533fs (c.1596del) pathogenic?

CDKL5 p.Thr533fs (c.1596del) is classified Likely pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-11-01). Absent from gnomAD; Associated with infantile spasms.

What condition is associated with CDKL5 p.Thr533fs (c.1596del)?

CDKL5 p.Thr533fs (c.1596del) is associated with infantile spasms (ClinVar).

How common is CDKL5 p.Thr533fs (c.1596del) in the general population?

CDKL5 p.Thr533fs (c.1596del) is absent from gnomAD (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CDKL5 p.Thr533fs

c.1596del · rs1555952078 · VCV547187

Likely pathogenic Single submitter

Classification

Likely 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

infantile spasms

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 8	GERP 1.3, phastCons 1

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.Thr533fs
Coding: c.1596del
MANE Select: NM_001323289
dbSNP: rs1555952078
Type: Deletion
Location: chrX:18604516 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 533: the 'disordered' region

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

Disease context

infantile spasms — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

Similar variants

CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
CDKL5 c.404-1G>C Pathogenic/Likely pathogenic ★★ same condition
CDKL5 c.99+1G>T Pathogenic/Likely pathogenic ★★ same condition
RS1 c.184+3207C>T Benign ★★ same condition
CDKL5 p.Gln830fs Likely pathogenic ★ same condition
CDKL5 p.Met448Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
CDKL5 p.His124fs Pathogenic ★★★ same type
CDKL5 p.Tyr941fs Pathogenic ★★★ same type

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-thr533fs (accessed [today's date]).

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