Is CPA6 p.Arg8= (c.24G>A) pathogenic?

CPA6 p.Arg8= (c.24G>A) is classified Likely benign in CPA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Very rare (popmax 0.000848%, nfe); Associated with febrile seizures, familial, 11.

What condition is associated with CPA6 p.Arg8= (c.24G>A)?

CPA6 p.Arg8= (c.24G>A) is associated with febrile seizures, familial, 11 (ClinVar).

How common is CPA6 p.Arg8= (c.24G>A) in the general population?

CPA6 p.Arg8= (c.24G>A) is very rare (popmax 0.000848%, nfe) (gnomAD).

CPA6 p.Arg8=

c.24G>A · rs777248963 · VCV1081645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, 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 assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.82, phastCons 1
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,682 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000684% 10/1,461,298 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.Arg8=
Coding: c.24G>A
MANE Select: NM_020361
dbSNP: rs777248963
Type: single nucleotide variant
Location: chr8:67746106 (GRCh38)
Gene constraint: LOEUF 1.338 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 90.93

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

Similar variants

CPA6 c.534+4A>G Uncertain significance ★★ same condition
CPA6 p.Arg128Ter Uncertain significance ★★ same condition
CPA6 p.Arg182Gln Uncertain significance ★★ ⚠ same condition
CPA6 p.Arg36Leu Uncertain significance ★★ ⚠ same condition
CPA6 p.Arg7His Uncertain significance ★★ ⚠ same condition
CPA6 p.Arg92Gln Uncertain significance ★★ ⚠ same condition
CPA6 p.Asn35Lys Uncertain significance ★★ ⚠ same condition
CPA6 p.Gln125Arg Uncertain significance ★★ ⚠ 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/cpa6-p-arg8 (accessed [today's date]).

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