Is AKAP9 p.Val124= (c.372G>A) pathogenic?

AKAP9 p.Val124= (c.372G>A) is classified Likely benign in AKAP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-04). Very rare (popmax 0.000425%, nfe); Associated with long QT syndrome.

What condition is associated with AKAP9 p.Val124= (c.372G>A)?

AKAP9 p.Val124= (c.372G>A) is associated with long QT syndrome (ClinVar).

How common is AKAP9 p.Val124= (c.372G>A) in the general population?

AKAP9 p.Val124= (c.372G>A) is very rare (popmax 0.000425%, nfe) (gnomAD).

AKAP9 p.Val124=

c.372G>A · VCV3702544

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

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 8.5	GERP 4.8, phastCons 1
Overall
CADD	11.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,176,280 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000343% 5/1,457,546 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.Val124=
Coding: c.372G>A
MANE Select: NM_005751
Type: single nucleotide variant
Location: chr7:91992178 (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 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
AKAP9 c.49-3T>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-val124 (accessed [today's date]).

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