Is CDKL5 p.Arg478fs (c.1432_1433insT) pathogenic?

CDKL5 p.Arg478fs (c.14321433insT) is classified Likely pathogenic in CDKL5 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-13). Absent from gnomAD; Associated with CDKL5 disorder.

What condition is associated with CDKL5 p.Arg478fs (c.1432_1433insT)?

CDKL5 p.Arg478fs (c.1432_1433insT) is associated with CDKL5 disorder (ClinVar).

How common is CDKL5 p.Arg478fs (c.1432_1433insT) in the general population?

CDKL5 p.Arg478fs (c.1432_1433insT) is absent from gnomAD (gnomAD).

CDKL5 p.Arg478fs

c.1432_1433insT · rs786204971 · VCV189558

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CDKL5 disorder

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 2.2	GERP -1.4, phastCons 0.78

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.Arg478fs
Coding: c.1432_1433insT
MANE Select: NM_001323289
dbSNP: rs786204971
Type: Insertion
Location: chrX:18604356 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 478: the 'disordered' region

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

Disease context

CDKL5 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDKL5 p.Glu93fs Pathogenic ★ same condition
CDKL5 p.Lys344delinsArgGln Uncertain significance ★ same condition
CDKL5 c.146-1G>A Pathogenic ★★★ same condition
CDKL5 p.Ala157Pro Likely pathogenic ★★★ same condition
CDKL5 p.Ala157Val Likely pathogenic ★★★ same condition
CDKL5 p.Ala40Val Pathogenic ★★★ same condition
CDKL5 p.Arg178Gln Pathogenic ★★★ same condition
CDKL5 p.Arg717= 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-arg478fs (accessed [today's date]).

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