Is CDKL5 p.Thr538fs (c.1612_1613del) pathogenic?

CDKL5 p.Thr538fs (c.16121613del) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-08). Absent from gnomAD.

How common is CDKL5 p.Thr538fs (c.1612_1613del) in the general population?

CDKL5 p.Thr538fs (c.1612_1613del) is absent from gnomAD (gnomAD).

CDKL5 p.Thr538fs

c.1612_1613del · rs2147160920 · VCV1335976

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 12 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	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.Thr538fs
Coding: c.1612_1613del
MANE Select: NM_001323289
dbSNP: rs2147160920
Type: Microsatellite
Location: chrX:18604534 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 538: the 'disordered' region

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

Similar variants

CDKL5 p.Thr538Ala Likely benign ★★★ same residue
CDKL5 p.Thr538Lys Uncertain significance ★ ⚠ same residue
CDKL5 p.Thr538= Likely benign ★ same residue
CDKL5 p.Thr538Met Likely benign ★ ⚠ 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

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-thr538fs (accessed [today's date]).

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