Is CACNA1D p.Pro2017= (c.6051G>A) pathogenic?

CACNA1D p.Pro2017= (c.6051G>A) is classified Benign in CACNA1D (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 5.38%, mid) — 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.Pro2017= (c.6051G>A)?

CACNA1D p.Pro2017= (c.6051G>A) is associated with aldosterone-producing adenoma with seizures and neurological abnormalities (ClinVar).

CACNA1D p.Pro2017=

Q: How common is CACNA1D p.Pro2017= (c.6051G>A) in the general population?

CACNA1D p.Pro2017= (c.6051G>A) is common (popmax 5.38%, mid) — 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.6051G>A · rs34388124 · VCV226477

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 5.38%, mid) — 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 -14	GERP -4.1
Overall
CADD	0.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.38% Middle Eastern · 326/6,062 alleles

Filtering AF 4.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.71%

Overall 3.41% 55,098/1,613,936 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.38%	19
Ashkenazi Jewishnot grpmax-eligible	5.32%	19
Finnishnot grpmax-eligible	4.06%	25
European (non-Finnish)	3.79%	26
Remaining individualsnot grpmax-eligible	3.22%	31
South Asian	2.38%	42
Admixed American	2.01%	50
Amishnot grpmax-eligible	1.75%	57
African / African-American	0.576%	174
East Asian	0.00668%	14,961

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.Pro2017=
Coding: c.6051G>A
MANE Select: NM_001128840
dbSNP: rs34388124
Type: single nucleotide variant
Location: chr3:53810157 (GRCh38)
Gene constraint: LOEUF 0.253 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.60 · 6 PDB

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.Pro2017Leu Uncertain significance ★★ ⚠ 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-pro2017 (accessed [today's date]).

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