Is CASK p.Ile18= (c.54C>T) pathogenic?

CASK p.Ile18= (c.54C>T) is classified Likely benign in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-26). Absent from gnomAD v4.1; Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.Ile18= (c.54C>T)?

CASK p.Ile18= (c.54C>T) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.Ile18= (c.54C>T) in the general population?

CASK p.Ile18= (c.54C>T) is absent from gnomAD v4.1 (gnomAD).

CASK p.Ile18=

c.54C>T · rs2148116044 · VCV1103806

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Intellectual disability, CASK-related, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.25	donor gain · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 2.9, phastCons 1
Overall
CADD	17.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CASK
Protein: p.Ile18=
Coding: c.54C>T
MANE Select: NM_001367721
dbSNP: rs2148116044
Type: single nucleotide variant
Location: chrX:41922935 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 18: the protein kinase domain; a binding site; a β-strand

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-ile18 (accessed [today's date]).

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