Is CASK p.Glu62Lys (c.184G>A) pathogenic?

CASK p.Glu62Lys (c.184G>A) is classified Likely pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-20). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with genetic developmental and epileptic encephalopathy.

What condition is associated with CASK p.Glu62Lys (c.184G>A)?

CASK p.Glu62Lys (c.184G>A) is associated with genetic developmental and epileptic encephalopathy (ClinVar).

How common is CASK p.Glu62Lys (c.184G>A) in the general population?

CASK p.Glu62Lys (c.184G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CASK p.Glu62Lys (c.184G>A)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

CASK p.Glu62Lys

c.184G>A · VCV4072125

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,156,574)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

genetic developmental and epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 4% in CASK
REVEL	0.846	moderately pathogenic-leaning
SaProt	LLR -14.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 286 kb · p 1e-25 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,156,574). 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: CASK
Protein: p.Glu62Lys
Coding: c.184G>A
MANE Select: NM_001367721
Type: single nucleotide variant
Location: chrX:41787272 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 62: the protein kinase domain; a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); an α-helix

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

Disease context

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

Similar variants

CASK p.Glu62fs Pathogenic ★ same residue
CASK c.1015+1G>A Pathogenic ★★ same type
CASK c.1315-1G>A Pathogenic/Likely pathogenic ★★ same type
CASK c.2317+1G>A Pathogenic/Likely pathogenic ★★ same type
CASK c.2317+5G>A Pathogenic/Likely pathogenic ★★ same type
CASK c.2521-2A>G Pathogenic/Likely pathogenic ★★ same type
CASK c.59+2T>C Pathogenic/Likely pathogenic ★★ same type
CASK p.Arg106Ter 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/cask-p-glu62lys (accessed [today's date]).

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