Is CPA6 p.Ala424= (c.1272T>C) pathogenic?

CPA6 p.Ala424= (c.1272T>C) is classified Likely benign in CPA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-18). Very rare (popmax 0.00237%, nfe); Associated with febrile seizures, familial, 11.

What condition is associated with CPA6 p.Ala424= (c.1272T>C)?

CPA6 p.Ala424= (c.1272T>C) is associated with febrile seizures, familial, 11 (ClinVar).

How common is CPA6 p.Ala424= (c.1272T>C) in the general population?

CPA6 p.Ala424= (c.1272T>C) is very rare (popmax 0.00237%, nfe) (gnomAD).

CPA6 p.Ala424=

c.1272T>C · rs763682412 · VCV744130

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Conditions

febrile seizures, familial, 11

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.55	GERP -3.7
Overall
CADD	6.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,180,010 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00173% 28/1,614,030 alleles · very rare

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: CPA6
Protein: p.Ala424=
Coding: c.1272T>C
dbSNP: rs763682412
Type: single nucleotide variant
Location: chr8:67422546 (GRCh38)

Full CPA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

febrile seizures, familial, 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/cpa6-p-ala424 (accessed [today's date]).

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