Is AKAP9 p.Ala853= (c.2559T>C) pathogenic?

AKAP9 p.Ala853= (c.2559T>C) is classified Likely benign in AKAP9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-01-29). Ultra-rare (popmax 0.0331%, mid); Associated with Cardiovascular phenotype.

What condition is associated with AKAP9 p.Ala853= (c.2559T>C)?

AKAP9 p.Ala853= (c.2559T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is AKAP9 p.Ala853= (c.2559T>C) in the general population?

AKAP9 p.Ala853= (c.2559T>C) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

AKAP9 p.Ala853=

c.2559T>C · rs762012353 · VCV702859

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

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 1.9	GERP 2.8, phastCons 1
Overall
CADD	10.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,044 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000621% 10/1,610,394 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,022
Admixed American	0.00673%	14,857
East Asian	0.00223%	44,780
European (non-Finnish)	0.000254%	392,998

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.Ala853=
Coding: c.2559T>C
MANE Select: NM_005751
dbSNP: rs762012353
Type: single nucleotide variant
Location: chr7:92002476 (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 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
AKAP9 c.576+5G>A 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-ala853 (accessed [today's date]).

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