Is AKAP9 p.Pro2964= (c.8892C>G) pathogenic?

AKAP9 p.Pro2964= (c.8892C>G) is classified Likely benign in AKAP9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-09). Very rare (popmax 0.00267%, afr); Associated with long QT syndrome.

What condition is associated with AKAP9 p.Pro2964= (c.8892C>G)?

AKAP9 p.Pro2964= (c.8892C>G) is associated with long QT syndrome (ClinVar).

How common is AKAP9 p.Pro2964= (c.8892C>G) in the general population?

AKAP9 p.Pro2964= (c.8892C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

AKAP9 p.Pro2964=

c.8892C>G · rs1172853201 · VCV1137623

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

long QT syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -5.8
Overall
CADD	4.337	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,882 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000558% 9/1,613,806 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,441
Admixed American	0.00167%	59,968
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000424%	235,982

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.Pro2964=
Coding: c.8892C>G
MANE Select: NM_005751
dbSNP: rs1172853201
Type: single nucleotide variant
Location: chr7:92085554 (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.Pro2964Ser 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
AKAP9 c.48+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-pro2964 (accessed [today's date]).

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