Is CASK p.Ser155= (c.465G>A) pathogenic?

CASK p.Ser155= (c.465G>A) is classified Benign/Likely benign in CASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-28). Very rare (popmax 0.0022%, amr); Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.Ser155= (c.465G>A)?

CASK p.Ser155= (c.465G>A) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.Ser155= (c.465G>A) in the general population?

CASK p.Ser155= (c.465G>A) is very rare (popmax 0.0022%, amr) (gnomAD).

CASK p.Ser155=

c.465G>A · rs1394766051 · VCV1976819

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, amr)

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 -5.6	GERP -0.72
Overall
CADD	0.676	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% Admixed American · 1/45,465 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000332% 4/1,203,555 alleles · very rare exomes 3/1,093,421 · genomes 1/110,134 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0022%	45,465
African / African-American	0.00177%	56,477
European (non-Finnish)	0.000225%	445,359

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.Ser155=
Coding: c.465G>A
MANE Select: NM_001367721
dbSNP: rs1394766051
Type: single nucleotide variant
Location: chrX:41671495 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 155: the protein kinase domain; a modified residue (phosphoserine; by autocatalysis); 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.Ser155Leu Likely pathogenic ★ same residue
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

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-ser155 (accessed [today's date]).

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