CACNA1E p.Ala702=
c.2106T>A · rs1654707390 · VCV2974584
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.85 | GERP -0.004, phastCons 0.014 |
| Overall | ||
| CADD | 11.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,702 alleles
Overall
6.84e-05%
1/1,461,114 alleles · very rare
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
- CACNA1E
- Protein
- p.Ala702=
- Coding
- c.2106T>A
- MANE Select
- NM_001205293
- dbSNP
- rs1654707390
- Type
- single nucleotide variant
- Location
- chr1:181724501 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.56 · 5 PDB
- Residue 702
- a UniProt-annotated variant site (in dee69); a UniProt-annotated variant site (in dee69; gain-of-function variant affecting channel activity; shifts the voltage dependence of activation toward more negative potentials and slows the fast inactivation time course); an α-helix
Similar variants
- CACNA1E p.Ala702Thr Pathogenic/Likely pathogenic ★★ same residue
- CACNA1E p.Ala702Gly Likely pathogenic ★ same residue
- CACNA1E p.Ala702Pro Likely pathogenic ★ same residue
- CACNA1E p.Ala702Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- CACNA1E p.Ala702Ser Pathogenic same residue
- CACNA1E p.Gly348Arg Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Ile603Leu Pathogenic/Likely pathogenic ★★ ⚠ 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/cacna1e-p-ala702 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown