Is AKAP1 p.Arg270Ser (c.810G>T) pathogenic?

AKAP1 p.Arg270Ser (c.810G>T) is classified Likely benign in AKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: likely benign (0.0893); Ultra-rare (popmax 0.0223%, eas).

How common is AKAP1 p.Arg270Ser (c.810G>T) in the general population?

AKAP1 p.Arg270Ser (c.810G>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about AKAP1 p.Arg270Ser (c.810G>T)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

AKAP1 p.Arg270Ser

c.810G>T · rs781204091 · VCV2405553

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -4.37	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 0.64	GERP -0.56, phastCons 0.058
Regional constraint	o/e 1.07	unconstrained · MANE · 508 bp · p 0.34 · regional, not allelic
Overall
CADD	0.83	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 0.0223% East Asian · 10/44,884 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00124% 20/1,614,094 alleles · ultra-rare exomes 17/1,461,876 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,488
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Admixed American	0.00167%	60,008

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.Arg270Ser
Coding: c.810G>T
MANE Select: NM_003488
dbSNP: rs781204091
Type: single nucleotide variant
Location: chr17:57106274 (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 c.1976-6A>G Benign ★★ same type
AKAP1 p.Ala218Thr Benign ★★ same type
AKAP1 p.Gly323Ser Benign ★★ same type
AKAP1 p.Pro475= 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-arg270ser (accessed [today's date]).

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