CACNA1I p.Pro940=
c.2820G>A · rs59624877 · VCV2653157
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0653%, afr)
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 -4.9 | GERP -3.4 |
| Overall | ||
| CADD | 7.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0653%
African / African-American · 49/75,028 alleles
Filtering AF
0.0507%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0455%
Overall
0.00552%
89/1,611,910 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0653% | 1,531 |
| Middle Eastern | 0.0496% | 2,018 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,404 |
| Admixed American | 0.00334% | 29,939 |
| European (non-Finnish) | 0.00237% | 42,112 |
| South Asian | 0.0011% | 90,844 |
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
- CACNA1I
- Protein
- p.Pro940=
- Coding
- c.2820G>A
- MANE Select
- NM_021096
- dbSNP
- rs59624877
- Type
- single nucleotide variant
- Location
- chr22:39661229 (GRCh38)
- Gene constraint
- LOEUF 0.525 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.94 · 4 PDB
Similar variants
- CACNA1I p.Arg1131Leu Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg1453Gln Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg1466Trp Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg2064His Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg791His Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg950Gln Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg965Cys Uncertain significance ★★ ⚠ same type
- CACNA1I p.Arg987Cys 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/cacna1i-p-pro940 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown