Is CACNA2D2 p.Trp45Ter (c.135G>A) pathogenic?

CACNA2D2 p.Trp45Ter (c.135G>A) is classified Likely pathogenic in CACNA2D2 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD v4.1; Associated with cerebellar atrophy with seizures and variable developmental delay.

What condition is associated with CACNA2D2 p.Trp45Ter (c.135G>A)?

CACNA2D2 p.Trp45Ter (c.135G>A) is associated with cerebellar atrophy with seizures and variable developmental delay (ClinVar).

How common is CACNA2D2 p.Trp45Ter (c.135G>A) in the general population?

CACNA2D2 p.Trp45Ter (c.135G>A) is absent from gnomAD v4.1 (gnomAD).

CACNA2D2 p.Trp45Ter

c.135G>A · rs2471323674 · VCV2585549

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,111,956)

Conditions

cerebellar atrophy with seizures and variable developmental delay

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 38
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -2.3, phastCons 0.003
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,111,956). 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.Trp45Ter
Coding: c.135G>A
MANE Select: NM_006030
dbSNP: rs2471323674
Type: single nucleotide variant
Location: chr3:50503289 (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

cerebellar atrophy with seizures and variable developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACNA2D2 p.Gln519Ter Pathogenic/Likely pathogenic ★★ same condition
CACNA2D2 c.1907+3A>C Uncertain significance ★★ same condition
CACNA2D2 c.785-3C>T Uncertain significance ★★ same condition
CACNA2D2 p.Arg1039Lys Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg422Cys Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg75Trp Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Glu106Lys Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Ile983Met 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-trp45ter (accessed [today's date]).

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