Is CDKL5 p.Glu98Ter (c.292G>T) pathogenic?

CDKL5 p.Glu98Ter (c.292G>T) is classified Pathogenic in CDKL5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-17). Absent from gnomAD v4.1.

How common is CDKL5 p.Glu98Ter (c.292G>T) in the general population?

CDKL5 p.Glu98Ter (c.292G>T) is absent from gnomAD v4.1 (gnomAD).

CDKL5 p.Glu98Ter

c.292G>T · rs2147142586 · VCV1193529

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,206,547)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 18
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,206,547). 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.Glu98Ter
Coding: c.292G>T
MANE Select: NM_001323289
dbSNP: rs2147142586
Type: single nucleotide variant
Location: chrX:18579857 (GRCh38)
Structure: AlphaFold pLDDT 53.76 · 3 PDB
Residue 98: 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.Ala98Glu Pathogenic ★★ same residue
CDKL5 c.146-1G>A Pathogenic ★★★ same type
CDKL5 p.Ala157Pro Likely pathogenic ★★★ same type
CDKL5 p.Ala157Val Likely pathogenic ★★★ same type
CDKL5 p.Ala40Val Pathogenic ★★★ same type
CDKL5 p.Arg178Gln Pathogenic ★★★ same type
CDKL5 p.Arg717= Likely pathogenic ★★★ same type
CDKL5 p.Arg948Ter 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-glu98ter (accessed [today's date]).

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