Is AKAP9 p.Arg3476= (c.10426A>C) pathogenic?

AKAP9 p.Arg3476= (c.10426A>C) is classified Benign/Likely benign in AKAP9 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 52.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with AKAP9 p.Arg3476= (c.10426A>C)?

AKAP9 p.Arg3476= (c.10426A>C) is associated with Cardiovascular phenotype, long QT syndrome, long QT syndrome 11 (ClinVar).

AKAP9 p.Arg3476=

Q: How common is AKAP9 p.Arg3476= (c.10426A>C) in the general population?

AKAP9 p.Arg3476= (c.10426A>C) is common (popmax 52.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.10426A>C · rs1063243 · VCV136344

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 52.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	acceptor gain, 27 bp away · raw score · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP 0.89, phastCons 1
Overall
CADD	8.875	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.8% African / African-American · 39,561/74,930 alleles

Filtering AF 52.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.2%

Overall 39% 629,501/1,613,192 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	54.3%	2
African / African-Americangrpmax	52.8%	2
Middle Eastern	42.5%	2
Remaining individualsnot grpmax-eligible	39.5%	3
South Asian	39%	3
European (non-Finnish)	38.9%	3
Finnishnot grpmax-eligible	38.6%	3
Admixed American	32.9%	3
Amishnot grpmax-eligible	23.1%	4
East Asian	18.3%	5

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AKAP9
Protein: p.Arg3476=
Coding: c.10426A>C
MANE Select: NM_005751
dbSNP: rs1063243
Type: single nucleotide variant
Location: chr7:92097613 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)

Full AKAP9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome long QT syndrome 11

Similar variants

AKAP9 p.Arg3476Ser Uncertain significance ★ ⚠ same residue
AKAP9 p.Arg3476Ter Uncertain significance ★ same residue
AKAP9 c.10713+4A>G Uncertain significance ★★ same condition
AKAP9 c.11686+4C>T Uncertain significance ★★ same condition
AKAP9 c.11687-2A>G Uncertain significance ★★ same condition
AKAP9 c.3838-4A>G Uncertain significance ★★ same condition
AKAP9 c.3952+2T>G Uncertain significance ★★ same condition
AKAP9 c.3953-3T>C 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/akap9-p-arg3476 (accessed [today's date]).

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