Is AKAP9 p.Arg1609= (c.4825A>C) pathogenic?

AKAP9 p.Arg1609= (c.4825A>C) is classified Benign/Likely benign in AKAP9 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-17). Rare (popmax 0.627%, mid); Associated with long QT syndrome 11.

What condition is associated with AKAP9 p.Arg1609= (c.4825A>C)?

AKAP9 p.Arg1609= (c.4825A>C) is associated with long QT syndrome 11, long QT syndrome (ClinVar).

How common is AKAP9 p.Arg1609= (c.4825A>C) in the general population?

AKAP9 p.Arg1609= (c.4825A>C) is rare (popmax 0.627%, mid) (gnomAD).

How is Romano-Ward syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AKAP9 p.Arg1609=

c.4825A>C · rs143473598 · VCV696357

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.627%, mid)

Conditions

long QT syndrome 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 3.7	GERP 2.6, phastCons 1
Overall
CADD	8.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.627% Middle Eastern · 38/6,062 alleles

Filtering AF 0.469% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.415%

Overall 0.0355% 573/1,614,092 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.627%	160
Admixed American	0.19%	526
Remaining individualsnot grpmax-eligible	0.088%	1,136
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
European (non-Finnish)	0.0262%	3,819
African / African-American	0.02%	5,002
South Asian	0.0198%	5,060
Finnishnot grpmax-eligible	0.00469%	21,340

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.Arg1609=
Coding: c.4825A>C
MANE Select: NM_005751
dbSNP: rs143473598
Type: single nucleotide variant
Location: chr7:92040806 (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

long QT syndrome 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome

For Romano-Ward syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

AKAP9 p.Arg1609Lys Benign/Likely benign ★★ same residue
AKAP9 p.Arg1609Gln Conflicting classifications of pathogenicity ★ 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-arg1609 (accessed [today's date]).

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