Is CPA6 p.Pro342= (c.1026C>G) pathogenic?

CPA6 p.Pro342= (c.1026C>G) is classified Conflicting classifications of pathogenicity in CPA6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2021-07-09). Ultra-rare (popmax 0.0211%, nfe); Associated with febrile seizures, familial, 11.

What condition is associated with CPA6 p.Pro342= (c.1026C>G)?

CPA6 p.Pro342= (c.1026C>G) is associated with febrile seizures, familial, 11 (ClinVar).

How common is CPA6 p.Pro342= (c.1026C>G) in the general population?

CPA6 p.Pro342= (c.1026C>G) is ultra-rare (popmax 0.0211%, nfe) (gnomAD).

CPA6 p.Pro342=

c.1026C>G · rs372964579 · VCV444756

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, 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 0.66	GERP -2.1, phastCons 1
Overall
CADD	4.241	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0211% European (non-Finnish) · 249/1,178,146 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0181%

Overall 0.0163% 262/1,611,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0211%	4,732
Remaining individualsnot grpmax-eligible	0.0128%	7,794
African / African-American	0.00668%	14,972

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.Pro342=
Coding: c.1026C>G
dbSNP: rs372964579
Type: single nucleotide variant
Location: chr8:67434053 (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-pro342 (accessed [today's date]).

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