Is CACNA2D2 p.Val293= (c.879C>T) pathogenic?

CACNA2D2 p.Val293= (c.879C>T) is classified Likely benign in CACNA2D2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). Absent from gnomAD v4.1; Associated with early-infantile DEE.

What condition is associated with CACNA2D2 p.Val293= (c.879C>T)?

CACNA2D2 p.Val293= (c.879C>T) is associated with early-infantile DEE (ClinVar).

How common is CACNA2D2 p.Val293= (c.879C>T) in the general population?

CACNA2D2 p.Val293= (c.879C>T) is absent from gnomAD v4.1 (gnomAD).

CACNA2D2 p.Val293=

c.879C>T · rs2106664141 · VCV1105115

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

early-infantile DEE

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.44 · evaluated, not missing
Pangolin	Δ0.21	loss · gain 0.03 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 5.2	GERP -0.23, phastCons 1
Overall
CADD	11.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CACNA2D2
Protein: p.Val293=
Coding: c.879C>T
MANE Select: NM_006030
dbSNP: rs2106664141
Type: single nucleotide variant
Location: chr3:50379982 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.48
Residue 293: the vwfa domain

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

Disease context

early-infantile DEE — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACNA2D2 c.2234+1G>A Likely pathogenic ★★ same condition
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.Ala1096Thr Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Ala253Thr Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg188Ser Uncertain significance ★★ ⚠ same condition
CACNA2D2 p.Arg422Cys 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-val293 (accessed [today's date]).

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