Is CACNA1A p.Pro511= (c.1533C>T) pathogenic?

CACNA1A p.Pro511= (c.1533C>T) is classified Likely benign in CACNA1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). Very rare (popmax 0.00501%, amr); Associated with developmental and epileptic encephalopathy, 42.

What condition is associated with CACNA1A p.Pro511= (c.1533C>T)?

CACNA1A p.Pro511= (c.1533C>T) is associated with developmental and epileptic encephalopathy, 42, episodic ataxia type 2 (ClinVar).

How common is CACNA1A p.Pro511= (c.1533C>T) in the general population?

CACNA1A p.Pro511= (c.1533C>T) is very rare (popmax 0.00501%, amr) (gnomAD).

CACNA1A p.Pro511=

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

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

c.1533C>T · rs751539123 · VCV1554410

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Conditions

developmental and epileptic encephalopathy, 42

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 0.84	GERP -5.7, phastCons 1
Overall
CADD	12.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00501% Admixed American · 3/59,868 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000373% 6/1,607,086 alleles · very rare exomes 6/1,454,842 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,956
African / African-American	0.00134%	74,876
European (non-Finnish)	0.00017%	587,120

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.Pro511=
Coding: c.1533C>T
MANE Select: NM_001127222
dbSNP: rs751539123
Type: single nucleotide variant
Location: chr19:13317134 (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

developmental and epileptic encephalopathy, 42 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: episodic ataxia type 2

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

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
CACNA1A c.3990-2A>G 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-pro511 (accessed [today's date]).

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