Is CACNA1A p.Ala2005= (c.6015C>T) pathogenic?

CACNA1A p.Ala2005= (c.6015C>T) is classified Likely benign in CACNA1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Very rare (popmax 0.00267%, sas); Associated with episodic ataxia type 2.

What condition is associated with CACNA1A p.Ala2005= (c.6015C>T)?

CACNA1A p.Ala2005= (c.6015C>T) is associated with episodic ataxia type 2, developmental and epileptic encephalopathy, 42 (ClinVar).

How common is CACNA1A p.Ala2005= (c.6015C>T) in the general population?

CACNA1A p.Ala2005= (c.6015C>T) is very rare (popmax 0.00267%, sas) (gnomAD).

How is Familial paroxysmal ataxia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CACNA1A p.Ala2005=

c.6015C>T · rs369675855 · VCV383723

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, sas)

Conditions

episodic ataxia type 2

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 0.25	GERP 0.58, phastCons 0.94
Overall
CADD	7.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% South Asian · 2/74,924 alleles

Filtering AF 0.000522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000381%

Overall 0.000858% 13/1,515,640 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00267%	37,462
European (non-Finnish)	0.000972%	102,875

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.Ala2005=
Coding: c.6015C>T
MANE Select: NM_001127222
dbSNP: rs369675855
Type: single nucleotide variant
Location: chr19:13212666 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.34 · 4 PDB
Residue 2005: a UniProt-annotated variant site (in ea2 and sca6); the 'disordered' region

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

Disease context

episodic ataxia type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 42

For Familial paroxysmal ataxia (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

CACNA1A p.Ala2005Thr Conflicting classifications of pathogenicity ★ ⚠ 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
CACNA1A c.3822+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>A Pathogenic ★★ same condition
CACNA1A c.3989+1G>T 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-ala2005 (accessed [today's date]).

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