CACNB4 p.Pro59=
c.177G>A · rs552093496 · VCV331635
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 -15 | GERP -3.9 |
| Overall | ||
| CADD | 5.733 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00279%
45/1,613,756 alleles · ultra-rare
exomes 39/1,461,504 · genomes 6/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| South Asian | 0.0154% | 6,505 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,799 |
| African / African-American | 0.004% | 25,007 |
| Admixed American | 0.00333% | 30,006 |
| European (non-Finnish) | 0.00178% | 56,177 |
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
- CACNB4
- Protein
- p.Pro59=
- Coding
- c.177G>A
- MANE Select
- NM_000726
- dbSNP
- rs552093496
- Type
- single nucleotide variant
- Location
- chr2:151883341 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.29 · 1 PDB
- Residue 59
- the 'disordered' region; a β-strand
Similar variants
- CACNB4 p.Ala12Ser Uncertain significance ★★ ⚠ same type
- CACNB4 p.Ala290Val Uncertain significance ★★ ⚠ same type
- CACNB4 p.Arg161Trp Uncertain significance ★★ ⚠ same type
- CACNB4 p.Arg437Ter Uncertain significance ★★ same type
- CACNB4 p.Arg453Leu Uncertain significance ★★ ⚠ same type
- CACNB4 p.Arg473Cys Uncertain significance ★★ same type
- CACNB4 p.Arg473His Uncertain significance ★★ ⚠ same type
- CACNB4 p.Arg506Gln 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/cacnb4-p-pro59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown