Is CAMK2B p.Pro523Ser (c.1567C>T) pathogenic?

CAMK2B p.Pro523Ser (c.1567C>T) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely benign (0.0682); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 54.

What condition is associated with CAMK2B p.Pro523Ser (c.1567C>T)?

CAMK2B p.Pro523Ser (c.1567C>T) is associated with intellectual developmental disorder, autosomal dominant 54 (ClinVar).

How common is CAMK2B p.Pro523Ser (c.1567C>T) in the general population?

CAMK2B p.Pro523Ser (c.1567C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2B p.Pro523Ser (c.1567C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

CAMK2B p.Pro523Ser

c.1567C>T · rs1703543682 · VCV2664914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder, autosomal dominant 54

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.58, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.35 · regional, not allelic
Overall
CADD	17.68	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAMK2B
Protein: p.Pro523Ser
Coding: c.1567C>T
MANE Select: NM_001220
dbSNP: rs1703543682
Type: single nucleotide variant
Location: chr7:44226546 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 523: a UniProt-annotated variant site (in mrd54); the 'disordered' region

Full CAMK2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder, autosomal dominant 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAMK2B p.Pro523Leu Benign/Likely benign ★★ ⚠ same residue
CAMK2B p.Pro523Ala Uncertain significance ★ ⚠ same residue
CAMK2B p.Pro523Arg Uncertain significance ★ ⚠ same residue
CAMK2B p.Pro523= Likely benign ★ same residue
CAMK2B p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
CAMK2B p.Glu110Lys Pathogenic ★★ same condition
CAMK2B p.Glu237Lys Pathogenic ★★ same condition
CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ 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/camk2b-p-pro523ser (accessed [today's date]).

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