Is CASK p.Tyr808= (c.2424C>T) pathogenic?

CASK p.Tyr808= (c.2424C>T) is classified Likely benign in CASK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-03). Very rare (popmax 0.00219%, amr); Associated with syndromic X-linked intellectual disability Najm type.

What condition is associated with CASK p.Tyr808= (c.2424C>T)?

CASK p.Tyr808= (c.2424C>T) is associated with syndromic X-linked intellectual disability Najm type, FG syndrome 4, anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is CASK p.Tyr808= (c.2424C>T) in the general population?

CASK p.Tyr808= (c.2424C>T) is very rare (popmax 0.00219%, amr) (gnomAD).

How is X-linked intellectual disability, Najm type inherited?

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

CASK p.Tyr808=

c.2424C>T · rs779629178 · VCV1438451

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Conditions

syndromic X-linked intellectual disability Najm type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.8	GERP -3.5
Overall
CADD	0.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00219% Admixed American · 1/45,762 alleles

Filtering AF 0.000569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000415%

Overall 0.00108% 13/1,203,233 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00422%	23,686
Admixed Americangrpmax	0.00219%	45,762
European (non-Finnish)	0.00112%	88,901

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr808=
Coding: c.2424C>T
MANE Select: NM_001367721
dbSNP: rs779629178
Type: single nucleotide variant
Location: chrX:41531103 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 808: 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; a β-strand

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

Disease context

syndromic X-linked intellectual disability Najm type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: FG syndrome 4 anemia, nonspherocytic hemolytic, due to G6PD deficiency

For X-linked intellectual disability, Najm type (Orphanet):

Inheritance: X-linked dominant
Onset: Infancy, Neonatal

Similar variants

CASK c.1015+1G>A Pathogenic ★★ same condition
CASK c.1315-1G>A Pathogenic/Likely pathogenic ★★ same condition
CASK c.2317+1G>A Pathogenic/Likely pathogenic ★★ same condition
CASK c.2317+5G>A Pathogenic/Likely pathogenic ★★ same condition
CASK c.2521-2A>G Pathogenic/Likely pathogenic ★★ same condition
CASK c.59+2T>C Pathogenic/Likely pathogenic ★★ same condition
CASK p.Arg106Ter Pathogenic ★★ same condition
CASK p.Arg255Cys 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/cask-p-tyr808 (accessed [today's date]).

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