CACNB4 p.Pro221=
c.663G>A · VCV3571485
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 -11 | GERP -3.7 |
| Overall | ||
| CADD | 5.935 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,054 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00149%
24/1,613,856 alleles · very rare
exomes 22/1,461,600 · genomes 2/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,211 |
| East Asian | 0.00446% | 22,440 |
| Admixed American | 0.00333% | 30,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00133% | 75,014 |
| European (non-Finnish) | 0.0011% | 90,756 |
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.Pro221=
- Coding
- c.663G>A
- MANE Select
- NM_000726
- Type
- single nucleotide variant
- Location
- chr2:151870567 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.29 · 1 PDB
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-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown