Is AKAP3 p.Ser150Pro (c.448T>C) pathogenic?

AKAP3 p.Ser150Pro (c.448T>C) is classified Uncertain significance in AKAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). AlphaMissense: likely benign (0.1847); Ultra-rare (popmax 0.0117%, amr).

How common is AKAP3 p.Ser150Pro (c.448T>C) in the general population?

AKAP3 p.Ser150Pro (c.448T>C) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about AKAP3 p.Ser150Pro (c.448T>C)?

AlphaMissense predicts likely benign (score 0.1847) — an in-silico prediction, not a clinical call.

AKAP3 p.Ser150Pro

c.448T>C · VCV3514994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1847	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.07	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 3.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 22 kb · p 0.012 · regional, not allelic
Overall
CADD	13.6	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 0.0117% Admixed American · 7/60,010 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00657% 106/1,614,058 alleles · ultra-rare exomes 98/1,461,878 · genomes 8/152,180 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
European (non-Finnish)	0.00805%	12,421
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00267%	37,459

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: AKAP3
Protein: p.Ser150Pro
Coding: c.448T>C
MANE Select: NM_001278309
Type: single nucleotide variant
Location: chr12:4628454 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 50.79

Full AKAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP3 p.Phe56= Benign ★★ same type
AKAP3 p.Val824= Benign ★★ same type
AKAP3 p.Cys15Tyr Likely pathogenic ★ ⚠ same type
AKAP3 p.Ala477Val Uncertain significance ★ ⚠ same type
AKAP3 p.Ala693Gly Uncertain significance ★ ⚠ same type
AKAP3 p.Ala810Thr Uncertain significance ★ ⚠ same type
AKAP3 p.Ala836Val Uncertain significance ★ ⚠ same type
AKAP3 p.Arg130His 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/akap3-p-ser150pro (accessed [today's date]).

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