Is CAMK2B p.Ser522Pro (c.1564T>C) pathogenic?

CAMK2B p.Ser522Pro (c.1564T>C) is classified Conflicting classifications of pathogenicity in CAMK2B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-08). AlphaMissense: likely benign (0.0598); Very rare (popmax 0.00275%, amr); Associated with Inborn genetic diseases.

What condition is associated with CAMK2B p.Ser522Pro (c.1564T>C)?

CAMK2B p.Ser522Pro (c.1564T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CAMK2B p.Ser522Pro (c.1564T>C) in the general population?

CAMK2B p.Ser522Pro (c.1564T>C) is very rare (popmax 0.00275%, amr) (gnomAD).

What do computational predictors say about CAMK2B p.Ser522Pro (c.1564T>C)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

CAMK2B p.Ser522Pro

c.1564T>C · rs2096481989 · VCV2800396

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00275%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -9.62	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 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.35 · regional, not allelic
Overall
CADD	16.38	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00275% Admixed American · 1/36,418 alleles

Filtering AF 0.000573% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000452%

Overall 0.000882% 13/1,473,926 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00275%	36,418
European (non-Finnish)	0.00107%	93,086

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: CAMK2B
Protein: p.Ser522Pro
Coding: c.1564T>C
MANE Select: NM_001220
dbSNP: rs2096481989
Type: single nucleotide variant
Location: chr7:44226549 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 522: 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

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

Similar variants

CAMK2B p.Ser522Phe Benign ★ ⚠ same residue
CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ same condition
CAMK2B p.Ala409Asp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Ala425Asp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Ala481Val Uncertain significance ★★ ⚠ same condition
CAMK2B p.Arg30Cys Uncertain significance ★★ ⚠ same condition
CAMK2B p.Arg534Trp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Asp12Glu 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/camk2b-p-ser522pro (accessed [today's date]).

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