Is CASK p.Asp334= (c.1002C>T) pathogenic?

CASK p.Asp334= (c.1002C>T) is classified Benign in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-21). Very rare (popmax 0.00176%, afr); Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.Asp334= (c.1002C>T)?

CASK p.Asp334= (c.1002C>T) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.Asp334= (c.1002C>T) in the general population?

CASK p.Asp334= (c.1002C>T) is very rare (popmax 0.00176%, afr) (gnomAD).

CASK p.Asp334=

c.1002C>T · VCV4737427

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00176%, afr)

Conditions

Intellectual disability, CASK-related, X-linked

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 7.3	GERP 1.9, phastCons 1
Overall
CADD	10.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% African / African-American · 1/56,931 alleles

Overall 0.000888% 1/112,627 alleles · very rare

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.Asp334=
Coding: c.1002C>T
MANE Select: NM_001367721
Type: single nucleotide variant
Location: chrX:41626617 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 334: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic)

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

Disease context

Intellectual disability, CASK-related, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Arg489Gln Pathogenic/Likely pathogenic ★★ same condition
CASK p.Ala359Val Uncertain significance ★★ ⚠ same condition
CASK p.Ala833Thr Uncertain significance ★★ ⚠ same condition
CASK p.Arg130Cys Uncertain significance ★★ ⚠ same condition
CASK p.Arg572His Uncertain significance ★★ ⚠ same condition
CASK p.Arg61Trp Uncertain significance ★★ ⚠ same condition
CASK p.Asp424Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp445Asn 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-asp334 (accessed [today's date]).

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