Is CDKL5 p.Arg735fs (c.2205_2206del) pathogenic?

CDKL5 p.Arg735fs (c.22052206del) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-30). Absent from gnomAD.

How common is CDKL5 p.Arg735fs (c.2205_2206del) in the general population?

CDKL5 p.Arg735fs (c.2205_2206del) is absent from gnomAD (gnomAD).

CDKL5 p.Arg735fs

c.2205_2206del · rs587783120 · VCV156648

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

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 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.54	GERP -4.1

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.Arg735fs
Coding: c.2205_2206del
MANE Select: NM_001323289
dbSNP: rs587783120
Type: Microsatellite
Location: chrX:18613202 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 735: the 'disordered' region; a UniProt-annotated variant site (in dee2)

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

Similar variants

CDKL5 p.Arg735delinsSerTer Pathogenic ★ same residue
CDKL5 p.Glu416fs Pathogenic ★★★ same type
CDKL5 p.Leu405fs Pathogenic ★★★ same type
RS1 p.Ile195_Ser196insIle Uncertain significance ★★★ same type
CDKL5 p.Cys152_Asp153delinsTer Pathogenic/Likely pathogenic ★★ same type
CDKL5 p.Glu77fs Pathogenic ★★ same type
CDKL5 p.His690_Ser691insTer Pathogenic ★★ same type
CDKL5 p.Leu67fs 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-arg735fs (accessed [today's date]).

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