CAMK2B p.Pro523=
c.1569G>T · rs546517142 · VCV1551977
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000269%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.32 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.5 |
| Overall | ||
| CADD | 4.207 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000269%
European (non-Finnish) · 3/1,115,036 alleles
Filtering AF
7.2e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2e-05%
Overall
0.000227%
3/1,319,254 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
- CAMK2B
- Protein
- p.Pro523=
- Coding
- c.1569G>T
- MANE Select
- NM_001220
- dbSNP
- rs546517142
- Type
- single nucleotide variant
- Location
- chr7:44226544 (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
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.Pro523Ser Uncertain significance ★ ⚠ same residue
- CAMK2B p.Pro523fs Conflicting classifications of pathogenicity ★ ⚠ same residue
- CAMK2B c.903+2T>C Likely pathogenic ★★ same type
- CAMK2B p.Arg29Ter Pathogenic/Likely pathogenic ★★ same type
- CAMK2B p.Glu110Lys 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/camk2b-p-pro523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown