Is CASK p.Glu804Lys (c.2410G>A) pathogenic?

CASK p.Glu804Lys (c.2410G>A) is classified Conflicting classifications of pathogenicity in CASK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-15). AlphaMissense: likely pathogenic (0.5874); Very rare (popmax 0.00296%, eas); Associated with Inborn genetic diseases.

What condition is associated with CASK p.Glu804Lys (c.2410G>A)?

CASK p.Glu804Lys (c.2410G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Glu804Lys (c.2410G>A) in the general population?

CASK p.Glu804Lys (c.2410G>A) is very rare (popmax 0.00296%, eas) (gnomAD).

What do computational predictors say about CASK p.Glu804Lys (c.2410G>A)?

AlphaMissense predicts likely pathogenic (score 0.5874) — an in-silico prediction, not a clinical call.

CASK p.Glu804Lys

c.2410G>A · rs751235198 · VCV968166

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.5874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5874	likely pathogenic
REVEL	0.269	benign-leaning
SaProt	LLR -13.29	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 22 kb · p 7.7e-05 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.00296% East Asian · 1/33,789 alleles

Filtering AF 0.000663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000484%

Overall 0.00108% 13/1,205,278 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,789
Remaining individualsnot grpmax-eligible	0.00211%	47,454
European (non-Finnish)	0.00123%	80,985

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CASK
Protein: p.Glu804Lys
Coding: c.2410G>A
MANE Select: NM_001367721
dbSNP: rs751235198
Type: single nucleotide variant
Location: chrX:41531117 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 804: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the guanylate kinase-like domain; the 'required for interaction with nrxn1 (via c-terminal tail)' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Ala300Thr Uncertain significance ★★ same condition
CASK p.Arg560Trp Uncertain significance ★★ ⚠ same condition
CASK p.Arg766Trp Uncertain significance ★★ same condition
CASK p.Asn31Ser Uncertain significance ★★ ⚠ same condition
CASK p.Asp330Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp498Gly Uncertain significance ★★ ⚠ same condition
CASK p.Glu662Asp Uncertain significance ★★ ⚠ same condition
CASK p.Gly21Asp Uncertain significance ★★ ⚠ 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/cask-p-glu804lys (accessed [today's date]).

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