Is AKAP9 p.Phe3045Ser (c.9134T>C) pathogenic?

AKAP9 p.Phe3045Ser (c.9134T>C) is classified Uncertain significance in AKAP9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.6288); Ultra-rare (popmax 0.0111%, eas); Associated with Cardiovascular phenotype.

What condition is associated with AKAP9 p.Phe3045Ser (c.9134T>C)?

AKAP9 p.Phe3045Ser (c.9134T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is AKAP9 p.Phe3045Ser (c.9134T>C) in the general population?

AKAP9 p.Phe3045Ser (c.9134T>C) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about AKAP9 p.Phe3045Ser (c.9134T>C)?

AlphaMissense predicts likely pathogenic (score 0.6288) — an in-silico prediction, not a clinical call.

AKAP9 p.Phe3045Ser

c.9134T>C · rs546876949 · VCV1765920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6288 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6288	likely pathogenic
REVEL	0.245	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 3.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.97 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,862 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,998 alleles · ultra-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.Phe3045Ser
Coding: c.9134T>C
MANE Select: NM_005751
dbSNP: rs546876949
Type: single nucleotide variant
Location: chr7:92086337 (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-phe3045ser (accessed [today's date]).

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