Is CDKL5 p.Arg717= (c.2151A>G) pathogenic?

CDKL5 p.Arg717= (c.2151A>G) is classified Likely pathogenic in CDKL5 (ClinVar, Expert panel, 5 submitters; last evaluated 2023-04-14). Absent from gnomAD v4.1; Associated with CDKL5 disorder.

What condition is associated with CDKL5 p.Arg717= (c.2151A>G)?

CDKL5 p.Arg717= (c.2151A>G) is associated with CDKL5 disorder, developmental and epileptic encephalopathy, 2 (ClinVar).

How common is CDKL5 p.Arg717= (c.2151A>G) in the general population?

CDKL5 p.Arg717= (c.2151A>G) is absent from gnomAD v4.1 (gnomAD).

CDKL5 p.Arg717=

c.2151A>G · rs886043453 · VCV286706

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 5 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CDKL5 disorder

ClinGen expert panel — Rett and Angelman-like Disorders VCEP

Likely Pathogenic for CDKL5 disorder. Applied ACMG criteria (verbatim):

PM2_Supporting PS4_Supporting PS2

Curation rationale (ClinGen, verbatim)

The p.Arg717= variant in CDKL5 occurs in the de novo state (biological parentage confirmed) in an individual (Invitae internal database )(PS2). The p.Arg717= variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in an individual (GeneDx internal database). The p.Arg717= variant has been observed in at least 2 individuals with neurological disease (Invitae and GeneDx internal database). The p.Arg717= variant in CDKL5 is absent from gnomAD (PM2_supporting). In summary, the p.Arg717= variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PS2, PS4_supporting, PM2_supporting).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Overall
CADD	19.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDKL5
Protein: p.Arg717=
Coding: c.2151A>G
MANE Select: NM_001323289
dbSNP: rs886043453
Type: single nucleotide variant
Location: chrX:18609569 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 717: 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

Also linked: developmental and epileptic encephalopathy, 2

Similar variants

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.Arg948Ter Pathogenic ★★★ same condition
CDKL5 p.Asn71Asp Likely pathogenic ★★★ same condition
CDKL5 p.Asp193Gly 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-arg717 (accessed [today's date]).

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