CACNB4 p.Pro217=
c.651G>A · VCV3385023
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0067%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.7 |
| Overall | ||
| CADD | 9.287 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0067%
European (non-Finnish) · 79/1,179,836 alleles
Filtering AF
0.00546%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00506%
Overall
0.00545%
88/1,613,710 alleles · very rare
exomes 87/1,461,578 · genomes 1/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0067% | 14,935 |
| South Asian | 0.00659% | 15,173 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
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.Pro217=
- Coding
- c.651G>A
- MANE Select
- NM_000726
- Type
- single nucleotide variant
- Location
- chr2:151870579 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.29 · 1 PDB
Similar variants
- CACNB4 p.Pro217Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown