Is CACNA1A p.Ala884Val (c.2651C>T) pathogenic?

CACNA1A p.Ala884Val (c.2651C>T) is classified Likely benign in CACNA1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.0918); Very rare (popmax 0.00134%, afr); Associated with developmental and epileptic encephalopathy, 42.

What condition is associated with CACNA1A p.Ala884Val (c.2651C>T)?

CACNA1A p.Ala884Val (c.2651C>T) is associated with developmental and epileptic encephalopathy, 42, episodic ataxia type 2 (ClinVar).

How common is CACNA1A p.Ala884Val (c.2651C>T) in the general population?

CACNA1A p.Ala884Val (c.2651C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CACNA1A p.Ala884Val (c.2651C>T)?

AlphaMissense predicts likely benign (score 0.0918) — an in-silico prediction, not a clinical call.

CACNA1A p.Ala884Val

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2651C>T · rs746582791 · VCV660911

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0918 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 42

Computational evidence

Protein change
AlphaMissense	0.0918	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -1.4, phastCons 0.97
Regional constraint	o/e 1.02	unconstrained · MANE · 17 kb · p 0.55 · regional, not allelic
Overall
CADD	20.9	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 0.00134% African / African-American · 1/74,532 alleles

Overall 6.99e-05% 1/1,429,834 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: CACNA1A
Protein: p.Ala884Val
Coding: c.2651C>T
MANE Select: NM_001127222
dbSNP: rs746582791
Type: single nucleotide variant
Location: chr19:13298982 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.34 · 4 PDB
Residue 884: the 'disordered' region

Full CACNA1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 42 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: episodic ataxia type 2

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

CACNA1A p.Ala884fs Pathogenic ★★ same residue
CACNA1A c.1082+1G>A Pathogenic ★★ same condition
CACNA1A c.1198+1G>A Pathogenic/Likely pathogenic ★★ same condition
CACNA1A c.2105-2A>G Likely pathogenic ★★ same condition
CACNA1A c.3692+1G>A Pathogenic/Likely pathogenic ★★ same condition
CACNA1A c.3822+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>T 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/cacna1a-p-ala884val (accessed [today's date]).

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