Is AKAP9 p.Ser27= (c.81G>A) pathogenic?

AKAP9 p.Ser27= (c.81G>A) is classified Benign/Likely benign in AKAP9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-09). Rare (popmax 0.1%, afr); Associated with long QT syndrome.

What condition is associated with AKAP9 p.Ser27= (c.81G>A)?

AKAP9 p.Ser27= (c.81G>A) is associated with long QT syndrome, long QT syndrome 11 (ClinVar).

How common is AKAP9 p.Ser27= (c.81G>A) in the general population?

AKAP9 p.Ser27= (c.81G>A) is rare (popmax 0.1%, afr) (gnomAD).

AKAP9 p.Ser27=

c.81G>A · rs145936668 · VCV518860

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, 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 -0.74	GERP -4, phastCons 0.009
Overall
CADD	4.341	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% African / African-American · 75/74,856 alleles

Filtering AF 0.0819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.00787% 127/1,613,594 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	998
Admixed American	0.0217%	4,612
Remaining individualsnot grpmax-eligible	0.0112%	8,927
European (non-Finnish)	0.00271%	36,872

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.Ser27=
Coding: c.81G>A
MANE Select: NM_005751
dbSNP: rs145936668
Type: single nucleotide variant
Location: chr7:91973743 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Residue 27: the 'disordered' region

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

Also linked: long QT syndrome 11

Similar variants

AKAP9 p.Ser27Trp Uncertain significance ★★ ⚠ same residue
AKAP9 p.Ser27Leu Benign/Likely benign ★★ 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.3952+2T>G Uncertain significance ★★ same condition
AKAP9 c.3953-3T>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-ser27 (accessed [today's date]).

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