Is AKAP1 p.Pro475Leu (c.1424C>T) pathogenic?

AKAP1 p.Pro475Leu (c.1424C>T) is classified Likely benign in AKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). AlphaMissense: likely benign (0.0751); Very rare (popmax 0.00223%, eas).

How common is AKAP1 p.Pro475Leu (c.1424C>T) in the general population?

AKAP1 p.Pro475Leu (c.1424C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AKAP1 p.Pro475Leu (c.1424C>T)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

AKAP1 p.Pro475Leu

c.1424C>T · rs1914918170 · VCV2526111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.57	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 -0.85	GERP -2
Regional constraint	o/e 0.81	unconstrained · MANE · 14 kb · p 5.3e-08 · regional, not allelic
Overall
CADD	0.043	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 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,866 alleles · very rare exomes 19/1,461,528 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	0.00136%	73,734
South Asian	0.0011%	91,076

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: AKAP1
Protein: p.Pro475Leu
Coding: c.1424C>T
MANE Select: NM_003488
dbSNP: rs1914918170
Type: single nucleotide variant
Location: chr17:57106888 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 57.02

Full AKAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP1 p.Pro475= Benign ★★ same residue
AKAP1 c.1976-6A>G Benign ★★ same type
AKAP1 p.Ala218Thr Benign ★★ same type
AKAP1 p.Gly323Ser Benign ★★ same type
AKAP1 p.Pro818= Benign ★★ same type
AKAP1 p.Ser330Gly Benign ★★ same type
AKAP1 p.Ser388= Benign ★★ same type
AKAP1 p.Thr521Ile Likely benign ★★ 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/akap1-p-pro475leu (accessed [today's date]).

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