CACNA1E p.Ile166=
c.498C>T · rs376114074 · VCV1648542
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, mid)
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 -11 | GERP -5.4 |
| Overall | ||
| CADD | 5.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
Middle Eastern · 3/5,932 alleles
Filtering AF
0.0171%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00186%
30/1,613,604 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0506% | 1,977 |
| East Asian | 0.029% | 3,454 |
| Admixed American | 0.00667% | 15,000 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,817 |
| European (non-Finnish) | 0.000593% | 168,554 |
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.Ile166=
- Coding
- c.498C>T
- MANE Select
- NM_001205293
- dbSNP
- rs376114074
- Type
- single nucleotide variant
- Location
- chr1:181511496 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.56 · 5 PDB
- Residue 166
- an α-helix
Similar variants
- CACNA1E p.Ile166Met Uncertain significance ★ ⚠ same residue
- CACNA1E p.Ala702Thr Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Gly348Arg Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Ile603Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- CACNA1E p.Ile701Val Pathogenic ★★ ⚠ same type
- CACNA1E p.Leu228Pro Pathogenic/Likely pathogenic ★★ same type
- CACNA1E p.Phe698Leu 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-ile166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown