CAMK2B p.Arg646=
c.1938C>T · rs761759252 · VCV1562607
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0264%, sas)
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 -13 | GERP -3.7 |
| Overall | ||
| CADD | 0.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0264%
South Asian · 24/91,014 alleles
Filtering AF
0.0181%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0154%
Overall
0.00558%
90/1,611,816 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0264% | 3,792 |
| Finnishnot grpmax-eligible | 0.00804% | 12,445 |
| African / African-American | 0.00799% | 12,509 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,614 |
| European (non-Finnish) | 0.00407% | 24,578 |
| Admixed American | 0.00334% | 29,973 |
| East Asian | 0.00223% | 44,862 |
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.Arg646=
- Coding
- c.1938C>T
- MANE Select
- NM_001220
- dbSNP
- rs761759252
- Type
- single nucleotide variant
- Location
- chr7:44220125 (GRCh38)
- Gene constraint
- LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 72.35 · 4 PDB
- Residue 646
- a UniProt-annotated variant site (in mrd54); a β-strand
Similar variants
- CAMK2B p.Arg646Cys Uncertain significance ★★ ⚠ same residue
- CAMK2B p.Arg646His Likely benign ★ ⚠ 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 p.Pro139Leu Pathogenic/Likely 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-arg646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown