CAMK2B p.Pro139=
c.417G>A · rs143953872 · VCV2657429
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.3 |
| Overall | ||
| CADD | 0.379 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/60,006 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.00112%
18/1,613,686 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 15,002 |
| Finnishnot grpmax-eligible | 0.00313% | 31,932 |
| East Asian | 0.00223% | 44,880 |
| South Asian | 0.0022% | 45,536 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 0.000678% | 147,474 |
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.Pro139=
- Coding
- c.417G>A
- MANE Select
- NM_001220
- dbSNP
- rs143953872
- Type
- single nucleotide variant
- Location
- chr7:44243525 (GRCh38)
- Gene constraint
- LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 72.35 · 4 PDB
- Residue 139
- the protein kinase domain; a UniProt-annotated variant site (in mrd54); a UniProt-annotated variant site (in mrd54; decreased protein abundance; increased autophosphorylation; decreased neuronal migration); an α-helix
Similar variants
- CAMK2B p.Pro139Leu Pathogenic/Likely pathogenic ★★ 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
- CAMK2B p.Glu237Lys Pathogenic ★★ same type
- CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ same type
- CAMK2B c.1059+1G>A Uncertain significance ★★ same type
- CAMK2B c.1597+1G>A Uncertain significance ★★ 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-pro139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown