Is AKAP9 p.Pro3530= (c.10590C>T) pathogenic?

AKAP9 p.Pro3530= (c.10590C>T) is classified Likely benign in AKAP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-11). Very rare (popmax 0.00134%, afr); Associated with Cardiovascular phenotype.

What condition is associated with AKAP9 p.Pro3530= (c.10590C>T)?

AKAP9 p.Pro3530= (c.10590C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is AKAP9 p.Pro3530= (c.10590C>T) in the general population?

AKAP9 p.Pro3530= (c.10590C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

AKAP9 p.Pro3530=

c.10590C>T · rs1426083577 · VCV1779307

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.16	GERP 0.51, phastCons 0.97
Overall
CADD	5.342	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,902 alleles

Overall 0.000657% 1/152,134 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: AKAP9
Protein: p.Pro3530=
Coding: c.10590C>T
MANE Select: NM_005751
dbSNP: rs1426083577
Type: single nucleotide variant
Location: chr7:92097777 (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.Pro3530Leu 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
AKAP9 c.5601+4A>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-pro3530 (accessed [today's date]).

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