Is CACNA1D p.Val309= (c.927A>G) pathogenic?

CACNA1D p.Val309= (c.927A>G) is classified Benign in CACNA1D (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele; Associated with aldosterone-producing adenoma with seizures and neurological abnormalities.

What condition is associated with CACNA1D p.Val309= (c.927A>G)?

CACNA1D p.Val309= (c.927A>G) is associated with aldosterone-producing adenoma with seizures and neurological abnormalities (ClinVar).

CACNA1D p.Val309=

Q: How common is CACNA1D p.Val309= (c.927A>G) in the general population?

CACNA1D p.Val309= (c.927A>G) is common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Primary hyperaldosteronism-seizures-neurological abnormalities syndrome inherited?

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

c.927A>G · rs33970402 · VCV226480

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 6.78%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

aldosterone-producing adenoma with seizures and neurological abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -2.9, phastCons 1
Overall
CADD	8.349	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.78% African / African-American · 5,083/75,016 alleles

Filtering AF 6.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.56%

Overall 0.377% 6,088/1,613,878 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.78%	15
Admixed American	0.585%	171
Remaining individualsnot grpmax-eligible	0.527%	190
Middle Eastern	0.488%	205
South Asian	0.0242%	4,139
European (non-Finnish)	0.0232%	4,306

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: CACNA1D
Protein: p.Val309=
Coding: c.927A>G
MANE Select: NM_001128840
dbSNP: rs33970402
Type: single nucleotide variant
Location: chr3:53666346 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.60 · 6 PDB
Residue 309: a β-strand

Full CACNA1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

aldosterone-producing adenoma with seizures and neurological abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary hyperaldosteronism-seizures-neurological abnormalities syndrome (Orphanet):

Inheritance: Not applicable
Onset: Infancy, Neonatal

Similar variants

CACNA1D p.Val309Ile Benign/Likely benign ★★ same residue
CACNA1D c.3786+5G>A Uncertain significance ★★ same condition
CACNA1D p.Ala1575Val Uncertain significance ★★ ⚠ same condition
CACNA1D p.Ala1766Pro Uncertain significance ★★ ⚠ same condition
CACNA1D p.Arg1013Gln Uncertain significance ★★ ⚠ same condition
CACNA1D p.Arg1946His Uncertain significance ★★ ⚠ same condition
CACNA1D p.Arg2021Cys Uncertain significance ★★ ⚠ same condition
CACNA1D p.Arg324His 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/cacna1d-p-val309 (accessed [today's date]).

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