Is AKAP9 p.Thr482= (c.1446A>G) pathogenic?

AKAP9 p.Thr482= (c.1446A>G) is classified Likely benign in AKAP9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-26). Ultra-rare (popmax 0.0187%, afr); Associated with long QT syndrome.

What condition is associated with AKAP9 p.Thr482= (c.1446A>G)?

AKAP9 p.Thr482= (c.1446A>G) is associated with long QT syndrome (ClinVar).

How common is AKAP9 p.Thr482= (c.1446A>G) in the general population?

AKAP9 p.Thr482= (c.1446A>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

AKAP9 p.Thr482=

c.1446A>G · rs374138966 · VCV1093409

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Conditions

long QT syndrome

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 1.1	GERP 2.6, phastCons 0.11
Overall
CADD	5.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,926 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00093% 15/1,613,702 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,352
European (non-Finnish)	8.48e-05%	1,179,764

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.Thr482=
Coding: c.1446A>G
MANE Select: NM_005751
dbSNP: rs374138966
Type: single nucleotide variant
Location: chr7:92001363 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AKAP9 p.Thr482fs Uncertain significance ★ same residue
AKAP9 p.Thr482Ile 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.3953-3T>C Uncertain significance ★★ same condition
AKAP9 c.405+3A>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-thr482 (accessed [today's date]).

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