Is CACNA1A p.Arg987Pro (c.2960G>C) pathogenic?

CACNA1A p.Arg987Pro (c.2960G>C) is classified Conflicting classifications of pathogenicity in CACNA1A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.2315); Ultra-rare (popmax 0.0296%, afr); Associated with Inborn genetic diseases.

What condition is associated with CACNA1A p.Arg987Pro (c.2960G>C)?

CACNA1A p.Arg987Pro (c.2960G>C) is associated with Inborn genetic diseases, episodic ataxia type 2, developmental and epileptic encephalopathy, 42 (ClinVar).

How common is CACNA1A p.Arg987Pro (c.2960G>C) in the general population?

CACNA1A p.Arg987Pro (c.2960G>C) is ultra-rare (popmax 0.0296%, afr) (gnomAD).

What do computational predictors say about CACNA1A p.Arg987Pro (c.2960G>C)?

AlphaMissense predicts likely benign (score 0.2315) — an in-silico prediction, not a clinical call.

CACNA1A p.Arg987Pro

c.2960G>C · rs955869211 · VCV387025

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2315 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2315	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -7.01	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 17 kb · p 0.55 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0296% African / African-American · 20/67,458 alleles

Filtering AF 0.0196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0164%

Overall 0.00142% 21/1,476,744 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0296%	3,373
South Asian	0.00133%	75,370

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.Arg987Pro
Coding: c.2960G>C
MANE Select: NM_001127222
dbSNP: rs955869211
Type: single nucleotide variant
Location: chr19:13298673 (GRCh38)
Gene constraint: LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.34 · 4 PDB
Residue 987: the 'disordered' region

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.Arg987Trp Uncertain significance ★★ ⚠ same residue
CACNA1A p.Arg987Gly Likely benign ★ 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

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-arg987pro (accessed [today's date]).

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