Is CDKL5 p.Ser191fs (c.566dup) pathogenic?

CDKL5 p.Ser191fs (c.566dup) is classified Likely pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-25). Absent from gnomAD.

How common is CDKL5 p.Ser191fs (c.566dup) in the general population?

CDKL5 p.Ser191fs (c.566dup) is absent from gnomAD (gnomAD).

CDKL5 p.Ser191fs

c.566dup · rs2147147959 · VCV1678739

Likely pathogenic Single submitter

Classification

Likely 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 9 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 2.5, 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.Ser191fs
Coding: c.566dup
MANE Select: NM_001323289
dbSNP: rs2147147959
Type: Duplication
Location: chrX:18587963 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 191: the protein kinase domain; an α-helix

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

Similar variants

RS1 p.Arg191Gln Uncertain significance ★★ ⚠ same residue
CDKL5 p.Ser191= Benign/Likely benign ★★ same residue
RS1 p.Arg191Trp Uncertain significance ★ ⚠ same residue
CDKL5 p.Ser438fs Pathogenic ★★★ same type
CDKL5 c.65dupG Pathogenic/Likely pathogenic ★★ same type
CDKL5 c.825+1dup Likely pathogenic ★★ same type
CDKL5 p.Ala166fs Pathogenic ★★ same type
CDKL5 p.Arg558fs Pathogenic/Likely 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-ser191fs (accessed [today's date]).

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