Is CACNA2D1 p.Val799= (c.2397T>A) pathogenic?

CACNA2D1 p.Val799= (c.2397T>A) is classified Conflicting classifications of pathogenicity in CACNA2D1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-10). Rare (popmax 0.142%, afr); Associated with Brugada syndrome.

What condition is associated with CACNA2D1 p.Val799= (c.2397T>A)?

CACNA2D1 p.Val799= (c.2397T>A) is associated with Brugada syndrome (ClinVar).

How common is CACNA2D1 p.Val799= (c.2397T>A) in the general population?

CACNA2D1 p.Val799= (c.2397T>A) is rare (popmax 0.142%, afr) (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

CACNA2D1 p.Val799=

c.2397T>A · rs191213592 · VCV373662

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.142%, afr)

Conditions

Brugada syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.93	acceptor gain · deltas
Pangolin	Δ0.42	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 0.25, phastCons 1
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% African / African-American · 100/70,428 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00746% 104/1,394,012 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.142%	704
Remaining individualsnot grpmax-eligible	0.00548%	18,233
Admixed American	0.00173%	57,818

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: CACNA2D1
Protein: p.Val799=
Coding: c.2397T>A
MANE Select: NM_000722
dbSNP: rs191213592
Type: single nucleotide variant
Location: chr7:81967662 (GRCh38)
Gene constraint: LOEUF 0.437 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.97 · 30 PDB
Residue 799: a disulfide bond

Full CACNA2D1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Brugada syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CACNA2D1 c.1662+3G>A Uncertain significance ★★ same condition
CACNA2D1 c.2574+3A>G Uncertain significance ★★ same condition
CACNA2D1 c.3160-1G>A Uncertain significance ★★ same condition
CACNA2D1 p.Ala1022Glu Uncertain significance ★★ ⚠ same condition
CACNA2D1 p.Ala104Thr Uncertain significance ★★ ⚠ same condition
CACNA2D1 p.Ala104Val Uncertain significance ★★ ⚠ same condition
CACNA2D1 p.Ala30Pro Uncertain significance ★★ ⚠ same condition
CACNA2D1 p.Ala321Thr 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/cacna2d1-p-val799 (accessed [today's date]).

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