Is CASK p.Pro610Thr (c.1828C>A) pathogenic?

CASK p.Pro610Thr (c.1828C>A) is classified Uncertain significance in CASK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-05-27). AlphaMissense: likely benign (0.0655); Very rare (popmax 0.00045%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CASK p.Pro610Thr (c.1828C>A)?

CASK p.Pro610Thr (c.1828C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CASK p.Pro610Thr (c.1828C>A) in the general population?

CASK p.Pro610Thr (c.1828C>A) is very rare (popmax 0.00045%, nfe) (gnomAD).

What do computational predictors say about CASK p.Pro610Thr (c.1828C>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

CASK p.Pro610Thr

c.1828C>A · rs2065150683 · VCV1780878

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00045%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 5,911 bp · p 0.8 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00045% European (non-Finnish) · 4/888,776 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000333% 4/1,202,610 alleles · very rare

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.Pro610Thr
Coding: c.1828C>A
MANE Select: NM_001367721
dbSNP: rs2065150683
Type: single nucleotide variant
Location: chrX:41555614 (GRCh38)
Structure: AlphaFold pLDDT 79.45 · 22 PDB
Residue 610: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASK p.Ala300Thr Uncertain significance ★★ ⚠ same condition
CASK p.Arg560Trp Uncertain significance ★★ ⚠ same condition
CASK p.Arg766Trp Uncertain significance ★★ ⚠ same condition
CASK p.Asn31Ser Uncertain significance ★★ ⚠ same condition
CASK p.Asp330Gly Uncertain significance ★★ ⚠ same condition
CASK p.Asp498Gly Uncertain significance ★★ ⚠ same condition
CASK p.Glu662Asp Uncertain significance ★★ ⚠ same condition
CASK p.Gly21Asp 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-pro610thr (accessed [today's date]).

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