Is CASK p.Ser602= (c.1806G>A) pathogenic?

CASK p.Ser602= (c.1806G>A) is classified Uncertain significance in CASK (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-29). Very rare (popmax 0.00176%, sas); Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.Ser602= (c.1806G>A)?

CASK p.Ser602= (c.1806G>A) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.Ser602= (c.1806G>A) in the general population?

CASK p.Ser602= (c.1806G>A) is very rare (popmax 0.00176%, sas) (gnomAD).

CASK p.Ser602=

c.1806G>A · rs780024880 · VCV1970326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00176%, sas)

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	Δ0.91	donor loss · deltas
Pangolin	Δ0.74	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00176% South Asian · 1/56,856 alleles

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

Overall 0.000274% 3/1,092,935 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00176%	56,856
European (non-Finnish)	0.000225%	445,351

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.Ser602=
Coding: c.1806G>A
MANE Select: NM_001367721
dbSNP: rs780024880
Type: single nucleotide variant
Location: chrX:41557032 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 602: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the 'required for interaction with nrxn1 (via c-terminal tail)' region; the 'disordered' region

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.Ser602Leu Uncertain significance ★★ ⚠ same residue
CASK p.Ser602Ala Likely benign ★ 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

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-ser602 (accessed [today's date]).

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