Is CASK p.Ser562fs (c.1683dup) pathogenic?

CASK p.Ser562fs (c.1683dup) is classified Pathogenic in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-01). Absent from gnomAD.

How common is CASK p.Ser562fs (c.1683dup) in the general population?

CASK p.Ser562fs (c.1683dup) is absent from gnomAD (gnomAD).

CASK p.Ser562fs

c.1683dup · rs2147151260 · VCV1338270

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CASK
Protein: p.Ser562fs
Coding: c.1683dup
MANE Select: NM_001367721
dbSNP: rs2147151260
Type: Duplication
Location: chrX:41559832 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 562: a UniProt-annotated variant site (found in a patient with epilepsy and pontocerebellar hypoplasia; likely pathogenic); the pdz domain; a β-strand; the 'required for interaction with nrxn1 (via c-terminal tail)' region

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

Similar variants

CASK p.Ser562= Benign/Likely benign ★★ same residue
CASK c.1504-6dup Benign/Likely benign ★★ same type
CASK c.1806+17dup Likely benign ★★ same type
CASK c.2521-11dup Benign/Likely benign ★★ same type
CASK c.1156-4408_1503+2676dup Likely pathogenic ★ same type
CASK c.1315-4_1315-1dup Likely pathogenic ★ same type
CASK p.Ala187fs Likely pathogenic ★ same type
CASK p.Asn666fs Pathogenic ★ same type

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-ser562fs (accessed [today's date]).

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