Is CACNA1E p.Pro824Ser (c.2470C>T) pathogenic?

CACNA1E p.Pro824Ser (c.2470C>T) is classified Benign/Likely benign in CACNA1E (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0769); Ultra-rare (popmax 0.0241%, amr); Associated with developmental and epileptic encephalopathy, 69.

What condition is associated with CACNA1E p.Pro824Ser (c.2470C>T)?

CACNA1E p.Pro824Ser (c.2470C>T) is associated with developmental and epileptic encephalopathy, 69 (ClinVar).

How common is CACNA1E p.Pro824Ser (c.2470C>T) in the general population?

CACNA1E p.Pro824Ser (c.2470C>T) is ultra-rare (popmax 0.0241%, amr) (gnomAD).

What do computational predictors say about CACNA1E p.Pro824Ser (c.2470C>T)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

CACNA1E p.Pro824Ser

c.2470C>T · rs1284163110 · VCV1314898

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

developmental and epileptic encephalopathy, 69

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -5.09	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 3.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 10 kb · p 0.093 · regional, not allelic
Overall
CADD	14.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0241% Admixed American · 12/49,726 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.000862% 12/1,392,822 alleles · ultra-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.Pro824Ser
Coding: c.2470C>T
MANE Select: NM_001205293
dbSNP: rs1284163110
Type: single nucleotide variant
Location: chr1:181732556 (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.Pro824= Likely benign ★★ same residue
CACNA1E p.Pro824Leu Uncertain significance ★ ⚠ same residue
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

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-pro824ser (accessed [today's date]).

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