Is CDKL5 p.Thr977fs (c.2927dup) pathogenic?

CDKL5 p.Thr977fs (c.2927dup) is classified Likely pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). Associated with developmental and epileptic encephalopathy, 2.

What condition is associated with CDKL5 p.Thr977fs (c.2927dup)?

CDKL5 p.Thr977fs (c.2927dup) is associated with developmental and epileptic encephalopathy, 2 (ClinVar).

How is CDKL5-deficiency disorder inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDKL5 p.Thr977fs

c.2927dup · VCV3776027

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

developmental and epileptic encephalopathy, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -0.73
Region caveats
Repeat context	tandem	ACTCCAGGTCCGAGGC simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CDKL5
Protein: p.Thr977fs
Coding: c.2927dup
MANE Select: NM_001323289 · reported on NM_003159
Type: Duplication
Location: chrX:18650536 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB

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

Disease context

developmental and epileptic encephalopathy, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CDKL5-deficiency disorder (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

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
CDKL5 p.Thr792fs Pathogenic/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-thr977fs (accessed [today's date]).

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