CACNA1E p.Ser1603=
c.4809C>T · rs762633305 · VCV2887737
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00858%, amr)
Conditions
1
Inborn genetic diseases
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 1.1 | GERP 0.17, phastCons 1 |
| Overall | ||
| CADD | 11.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00858%
Admixed American · 5/58,244 alleles
Filtering AF
0.00333%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00212%
Overall
0.000447%
7/1,566,882 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00858% | 11,649 |
| European (non-Finnish) | 0.000175% | 573,026 |
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.Ser1603=
- Coding
- c.4809C>T
- MANE Select
- NM_001205293
- dbSNP
- rs762633305
- Type
- single nucleotide variant
- Location
- chr1:181763525 (GRCh38)
- Gene constraint
- LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.56 · 5 PDB
- Residue 1603
- a UniProt-annotated variant site (in dee69; uncertain significance); an α-helix
Similar variants
- CACNA1E p.Gly352Arg Pathogenic/Likely pathogenic ★★ same condition
- CACNA1E p.Ala487Ser Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Ala740Val Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Arg2059Trp Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Arg2154Ser Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Arg2156Cys Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Arg59Pro Uncertain significance ★★ ⚠ same condition
- CACNA1E p.Arg772Gln 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-ser1603 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown