Is CASK p.Leu912= (c.2736C>T) pathogenic?

CASK p.Leu912= (c.2736C>T) is classified Benign in CASK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). Very rare (popmax 0.00296%, eas); Associated with Intellectual disability, CASK-related, X-linked.

What condition is associated with CASK p.Leu912= (c.2736C>T)?

CASK p.Leu912= (c.2736C>T) is associated with Intellectual disability, CASK-related, X-linked (ClinVar).

How common is CASK p.Leu912= (c.2736C>T) in the general population?

CASK p.Leu912= (c.2736C>T) is very rare (popmax 0.00296%, eas) (gnomAD).

CASK p.Leu912=

c.2736C>T · rs147125272 · VCV2123336

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP 1.7, phastCons 1
Overall
CADD	5.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,771 alleles

Overall 0.000248% 3/1,207,628 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00296%	33,771
Admixed American	0.00219%	45,725
African / African-American	0.00175%	56,998

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.Leu912=
Coding: c.2736C>T
dbSNP: rs147125272
Type: single nucleotide variant
Location: chrX:41520465 (GRCh38)

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

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-leu912 (accessed [today's date]).

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