CACNA1E p.Phe1279=
c.3837C>T · rs41315709 · VCV1240675
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.7 | GERP -3.5 |
| Overall | ||
| CADD | 1.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
European (non-Finnish) · 1,589/1,179,642 alleles
Filtering AF
0.129%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.127%
Overall
0.108%
1,746/1,613,592 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.135% | 742 |
| Remaining individualsnot grpmax-eligible | 0.11% | 905 |
| Finnishnot grpmax-eligible | 0.0688% | 1,454 |
| African / African-American | 0.036% | 2,780 |
| Admixed American | 0.02% | 5,001 |
| Middle Eastern | 0.0165% | 6,060 |
| East Asian | 0.00668% | 14,961 |
| South Asian | 0.0011% | 90,986 |
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.Phe1279=
- Coding
- c.3837C>T
- MANE Select
- NM_001205293
- dbSNP
- rs41315709
- Type
- single nucleotide variant
- Location
- chr1:181755245 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.56 · 5 PDB
- Residue 1279
- a UniProt-annotated variant site (in dee69; uncertain significance); an α-helix
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-phe1279 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown