Is CACNA2D2 p.Ala286fs (c.851dup) pathogenic?

CACNA2D2 p.Ala286fs (c.851dup) is classified Pathogenic in CACNA2D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-13). Absent from gnomAD; Associated with developmental and epileptic encephalopathy.

What condition is associated with CACNA2D2 p.Ala286fs (c.851dup)?

CACNA2D2 p.Ala286fs (c.851dup) is associated with developmental and epileptic encephalopathy (ClinVar).

How common is CACNA2D2 p.Ala286fs (c.851dup) in the general population?

CACNA2D2 p.Ala286fs (c.851dup) is absent from gnomAD (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

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

CACNA2D2 p.Ala286fs

c.851dup · rs1575603683 · VCV653393

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

developmental and epileptic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CACNA2D2
Protein: p.Ala286fs
Coding: c.851dup
MANE Select: NM_006030
dbSNP: rs1575603683
Type: Duplication
Location: chr3:50380009 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.48

Full CACNA2D2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

CACNA2D2 p.Trp45_Leu46dup Uncertain significance ★★ same condition
CACNA2D2 c.842+6C>T Uncertain significance ★★ same condition
CACNA2D2 p.Ala1096Val Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Ala582Val Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Ala753Thr Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg102Trp Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg1039Lys Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg149Cys 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/cacna2d2-p-ala286fs (accessed [today's date]).

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