Is CACNA2D1 p.Asp1027= (c.3081C>T) pathogenic?

CACNA2D1 p.Asp1027= (c.3081C>T) is classified Likely benign in CACNA2D1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-16). Rare (popmax 0.124%, sas); Associated with Cardiovascular phenotype.

What condition is associated with CACNA2D1 p.Asp1027= (c.3081C>T)?

CACNA2D1 p.Asp1027= (c.3081C>T) is associated with Cardiovascular phenotype, Brugada syndrome (ClinVar).

How common is CACNA2D1 p.Asp1027= (c.3081C>T) in the general population?

CACNA2D1 p.Asp1027= (c.3081C>T) is rare (popmax 0.124%, sas) (gnomAD).

CACNA2D1 p.Asp1027=

c.3081C>T · rs568821967 · VCV1146757

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.124%, sas)

Conditions

Cardiovascular phenotype

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>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.18	GERP -2.2, phastCons 0.002
Overall
CADD	8.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.124% South Asian · 113/90,868 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0987%

Overall 0.0112% 180/1,604,294 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.124%	804
East Asian	0.0402%	2,488
Remaining individualsnot grpmax-eligible	0.00966%	10,356
Admixed American	0.00668%	14,965
European (non-Finnish)	0.00324%	30,825
African / African-American	0.00134%	74,850

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.Asp1027=
Coding: c.3081C>T
MANE Select: NM_000722
dbSNP: rs568821967
Type: single nucleotide variant
Location: chr7:81959353 (GRCh38)
Gene constraint: LOEUF 0.437 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.97 · 30 PDB
Residue 1027: a disulfide bond

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Brugada syndrome

Similar variants

CACNA2D1 p.Asp1027Glu Uncertain significance ★ ⚠ same residue
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

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-asp1027 (accessed [today's date]).

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