Is CDKL5 p.Gln1012fs (c.3034del) pathogenic?

CDKL5 p.Gln1012fs (c.3034del) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Gln1012fs (c.3034del)?

CDKL5 p.Gln1012fs (c.3034del) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How is CDKL5-deficiency disorder inherited?

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

CDKL5 p.Gln1012fs

c.3034del · VCV3764575

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.37	GERP -3.6

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

Variant & gene context

Gene: CDKL5
Protein: p.Gln1012fs
Coding: c.3034del
MANE Select: NM_001323289 · reported on NM_001037343
Type: Deletion
Location: chrX:18653483 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB

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.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
CDKL5 p.Glu55fs Pathogenic/Likely 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-gln1012fs (accessed [today's date]).

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