Is CDKL5 p.His338fs (c.1011dup) pathogenic?

CDKL5 p.His338fs (c.1011dup) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-07). Absent from gnomAD; Associated with Angelman syndrome-like.

What condition is associated with CDKL5 p.His338fs (c.1011dup)?

CDKL5 p.His338fs (c.1011dup) is associated with Angelman syndrome-like, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.His338fs (c.1011dup) in the general population?

CDKL5 p.His338fs (c.1011dup) is absent from gnomAD (gnomAD).

CDKL5 p.His338fs

c.1011dup · rs2147160162 · VCV1451469

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

Angelman syndrome-like

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 6	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.His338fs
Coding: c.1011dup
MANE Select: NM_001323289
dbSNP: rs2147160162
Type: Duplication
Location: chrX:18603934 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 338: the 'disordered' region

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

Disease context

Angelman syndrome-like — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

CDKL5 p.His338Tyr Uncertain significance ★ ⚠ same residue
CDKL5 c.65dupG Pathogenic/Likely pathogenic ★★ same condition
CDKL5 c.825+1dup Likely pathogenic ★★ same condition
CDKL5 p.Ala166fs Pathogenic ★★ same condition
CDKL5 p.Arg558fs Pathogenic/Likely pathogenic ★★ same condition
CDKL5 p.Asn293fs Pathogenic ★★ same condition
CDKL5 p.Glu170fs Likely pathogenic ★★ same condition
CDKL5 p.Leu184fs 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-his338fs (accessed [today's date]).

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