CACNA1E p.Ser1069=
c.3207C>T · rs200952541 · VCV1168381
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
rare (popmax 0.372%, nfe)
Conditions
1
developmental and epileptic encephalopathy, 69
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 -5.8 | GERP -3.8 |
| Overall | ||
| CADD | 1.685 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.372%
European (non-Finnish) · 4,359/1,171,826 alleles
Filtering AF
0.363%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.359%
Overall
0.307%
4,905/1,597,472 alleles · rare
exomes 4,660/1,445,196 · genomes 245/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.372% | 269 |
| South Asian | 0.311% | 322 |
| Remaining individualsnot grpmax-eligible | 0.228% | 438 |
| African / African-American | 0.0793% | 1,262 |
| Admixed American | 0.0678% | 1,474 |
| Finnishnot grpmax-eligible | 0.0455% | 2,198 |
| Middle Eastern | 0.0335% | 2,988 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00346% | 28,888 |
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.Ser1069=
- Coding
- c.3207C>T
- MANE Select
- NM_001205293
- dbSNP
- rs200952541
- Type
- single nucleotide variant
- Location
- chr1:181733695 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.56 · 5 PDB
- Residue 1069
- a UniProt-annotated variant site (in dee69; uncertain significance)
Similar variants
- CACNA1E p.Ala702Thr Pathogenic/Likely pathogenic ★★ same condition
- CACNA1E p.Gly348Arg Pathogenic/Likely pathogenic ★★ same condition
- CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same condition
- CACNA1E p.Ile603Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CACNA1E p.Ile701Val Pathogenic ★★ ⚠ same condition
- CACNA1E p.Leu228Pro Pathogenic/Likely pathogenic ★★ same condition
- CACNA1E p.Phe698Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
- CACNA1E c.3719+1G>A Uncertain significance ★★ same condition
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-ser1069 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown