Is CDKL5 p.Asn129fs (c.386del) pathogenic?

CDKL5 p.Asn129fs (c.386del) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-28). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Asn129fs (c.386del)?

CDKL5 p.Asn129fs (c.386del) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Asn129fs (c.386del) in the general population?

CDKL5 p.Asn129fs (c.386del) 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.Asn129fs

c.386del · rs1602271718 · VCV803717

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 6 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, 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.Asn129fs
Coding: c.386del
MANE Select: NM_001323289
dbSNP: rs1602271718
Type: Deletion
Location: chrX:18579950 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 129: the protein kinase domain

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

RS1 p.Glu129del Uncertain significance ★ 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
CDKL5 p.Arg943fs Likely pathogenic ★★ same condition
CDKL5 p.Gln891fs 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-asn129fs (accessed [today's date]).

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