Is CACNA1A p.Pro9= (c.27G>T) pathogenic?

CACNA1A p.Pro9= (c.27G>T) is classified Likely benign in CACNA1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-13). Ultra-rare (popmax 0.0126%, afr); Associated with Inborn genetic diseases.

What condition is associated with CACNA1A p.Pro9= (c.27G>T)?

CACNA1A p.Pro9= (c.27G>T) is associated with Inborn genetic diseases, episodic ataxia type 2, developmental and epileptic encephalopathy, 42 (ClinVar).

How common is CACNA1A p.Pro9= (c.27G>T) in the general population?

CACNA1A p.Pro9= (c.27G>T) is ultra-rare (popmax 0.0126%, afr) (gnomAD).

CACNA1A p.Pro9=

c.27G>T · rs547576283 · VCV507058

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, afr)

Conditions

Inborn genetic diseases

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 2.2	GERP -0.41, phastCons 1
Overall
CADD	15.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0126% African / African-American · 9/71,258 alleles

Filtering AF 0.00652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00489%

Overall 0.000802% 12/1,496,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0126%	7,918
Admixed American	0.00477%	20,944
Remaining individualsnot grpmax-eligible	0.00173%	57,840

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: CACNA1A
Protein: p.Pro9=
Coding: c.27G>T
MANE Select: NM_001127222
dbSNP: rs547576283
Type: single nucleotide variant
Location: chr19:13506198 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.34 · 4 PDB

Full CACNA1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: episodic ataxia type 2 developmental and epileptic encephalopathy, 42

Similar variants

CACNA1A p.Pro9Leu Uncertain significance ★★ ⚠ same residue
CACNA1A p.Pro9Ser Uncertain significance ★★ ⚠ same residue
CACNA1A p.Pro9Arg Uncertain significance ★ ⚠ same residue
HPCA p.Arg9Gln Uncertain significance ★ ⚠ same residue
CACNA1A c.1082+1G>A Pathogenic ★★ same condition
CACNA1A c.1198+1G>A Pathogenic/Likely pathogenic ★★ same condition
CACNA1A c.2105-2A>G Likely pathogenic ★★ same condition
CACNA1A c.3692+1G>A Pathogenic/Likely pathogenic ★★ 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/cacna1a-p-pro9 (accessed [today's date]).

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