Is AKAP12 p.Pro15Arg (c.44C>G) pathogenic?

AKAP12 p.Pro15Arg (c.44C>G) is classified Uncertain significance in AKAP12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.1127); Ultra-rare (popmax 0.0284%, afr).

How common is AKAP12 p.Pro15Arg (c.44C>G) in the general population?

AKAP12 p.Pro15Arg (c.44C>G) is ultra-rare (popmax 0.0284%, afr) (gnomAD).

What do computational predictors say about AKAP12 p.Pro15Arg (c.44C>G)?

AlphaMissense predicts likely benign (score 0.1127) — an in-silico prediction, not a clinical call.

AKAP12 p.Pro15Arg

c.44C>G · rs898508650 · VCV3105121

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1127 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1127	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 0.98
Regional constraint	o/e 0.98	unconstrained · MANE · 111 kb · p 0.55 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% African / African-American · 19/66,794 alleles

Filtering AF 0.0185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.00141% 20/1,420,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0284%	3,515
Admixed American	0.00296%	33,764

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: AKAP12
Protein: p.Pro15Arg
Coding: c.44C>G
MANE Select: NM_005100
dbSNP: rs898508650
Type: single nucleotide variant
Location: chr6:151240606 (GRCh38)
Gene constraint: LOEUF 0.496 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 40.98
Residue 15: the 'disordered' region

Full AKAP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP12 p.Ala1074Val Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1081Asp Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1141Thr Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1145Asp Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1145Thr Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1201Thr Uncertain significance ★ ⚠ same type
AKAP12 p.Ala129Val Uncertain significance ★ ⚠ same type
AKAP12 p.Ala1303Val Uncertain significance ★ ⚠ same type

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/akap12-p-pro15arg (accessed [today's date]).

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