CACNA1B p.Pro2139=
c.6417G>A · rs763000710 · VCV2421339
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0048%, eas)
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 -9.7 | |
| Overall | ||
| CADD | 0.051 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0048%
East Asian · 2/41,640 alleles
Filtering AF
0.0016%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000942%
Overall
0.000832%
13/1,561,936 alleles · very rare
exomes 10/1,409,854 · genomes 3/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0048% | 20,820 |
| South Asian | 0.00472% | 21,201 |
| African / African-American | 0.00273% | 36,675 |
| Finnishnot grpmax-eligible | 0.00166% | 60,416 |
| European (non-Finnish) | 0.000347% | 288,376 |
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
- CACNA1B
- Protein
- p.Pro2139=
- Coding
- c.6417G>A
- MANE Select
- NM_000718
- dbSNP
- rs763000710
- Type
- single nucleotide variant
- Location
- chr9:138120809 (GRCh38)
- Gene constraint
- LOEUF 0.425 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 60.66 · 7 PDB
- Residue 2139
- a UniProt-annotated variant site (in nedneh); the 'disordered' region
Similar variants
- CACNA1B p.Pro2139Leu Uncertain significance ★★ ⚠ same residue
- CACNA1B p.Arg2102Ter Pathogenic/Likely pathogenic ★★ same type
- CACNA1B p.Ala1161Thr Uncertain significance ★★ ⚠ same type
- CACNA1B p.Ala1556Val Uncertain significance ★★ ⚠ same type
- CACNA1B p.Ala1999Val Uncertain significance ★★ same type
- CACNA1B p.Ala2080Thr Uncertain significance ★★ ⚠ same type
- CACNA1B p.Ala2214Thr Uncertain significance ★★ ⚠ same type
- CACNA1B p.Ala2237Thr 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/cacna1b-p-pro2139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown