Is AKAP9 p.Arg3450= (c.10348C>A) pathogenic?

AKAP9 p.Arg3450= (c.10348C>A) is classified Likely benign in AKAP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). Ultra-rare (popmax 0.0373%, sas); Associated with Cardiovascular phenotype.

What condition is associated with AKAP9 p.Arg3450= (c.10348C>A)?

AKAP9 p.Arg3450= (c.10348C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is AKAP9 p.Arg3450= (c.10348C>A) in the general population?

AKAP9 p.Arg3450= (c.10348C>A) is ultra-rare (popmax 0.0373%, sas) (gnomAD).

AKAP9 p.Arg3450=

c.10348C>A · rs770593631 · VCV3224999

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, sas)

Conditions

Cardiovascular phenotype

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 0.1	GERP -0.34, phastCons 0.18
Overall
CADD	4.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% South Asian · 34/91,040 alleles

Filtering AF 0.0274% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.00229% 37/1,613,694 alleles · ultra-rare exomes 37/1,461,444 · genomes 0/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0373%	2,678
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)	8.47e-05%	1,179,966

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.Arg3450=
Coding: c.10348C>A
MANE Select: NM_005751
dbSNP: rs770593631
Type: single nucleotide variant
Location: chr7:92097307 (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

Similar variants

AKAP9 p.Arg3450Gln Uncertain significance ★★ ⚠ same residue
AKAP9 p.Arg3450Ter Uncertain significance ★ same residue
AKAP9 c.11687-2A>G Uncertain significance ★★ same condition
AKAP9 c.3953-3T>C Uncertain significance ★★ same condition
AKAP9 c.5058+2T>C Uncertain significance ★★ same condition
AKAP9 c.5162+3A>G Uncertain significance ★★ same condition
AKAP9 c.5162+4T>A Uncertain significance ★★ same condition
AKAP9 c.5162+5A>G 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-arg3450 (accessed [today's date]).

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