Is CACNA1E p.Ala796Val (c.2387C>T) pathogenic?

CACNA1E p.Ala796Val (c.2387C>T) is classified Uncertain significance in CACNA1E (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-21). AlphaMissense: likely benign (0.1046); Very rare (popmax 0.00119%, sas); Associated with developmental and epileptic encephalopathy, 69.

What condition is associated with CACNA1E p.Ala796Val (c.2387C>T)?

CACNA1E p.Ala796Val (c.2387C>T) is associated with developmental and epileptic encephalopathy, 69 (ClinVar).

How common is CACNA1E p.Ala796Val (c.2387C>T) in the general population?

CACNA1E p.Ala796Val (c.2387C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about CACNA1E p.Ala796Val (c.2387C>T)?

AlphaMissense predicts likely benign (score 0.1046) — an in-silico prediction, not a clinical call.

CACNA1E p.Ala796Val

c.2387C>T · rs1320817023 · VCV1699002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1046 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 69

Computational evidence

Protein change
AlphaMissense	0.1046	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.093 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,038 alleles

Overall 7.15e-05% 1/1,399,022 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.Ala796Val
Coding: c.2387C>T
MANE Select: NM_001205293
dbSNP: rs1320817023
Type: single nucleotide variant
Location: chr1:181732473 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.56 · 5 PDB

Full CACNA1E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 69 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ala796val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown