Is AKAP13 p.Arg367His (c.1100G>A) pathogenic?

AKAP13 p.Arg367His (c.1100G>A) is classified Likely benign in AKAP13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0602); Ultra-rare (popmax 0.0231%, sas).

How common is AKAP13 p.Arg367His (c.1100G>A) in the general population?

AKAP13 p.Arg367His (c.1100G>A) is ultra-rare (popmax 0.0231%, sas) (gnomAD).

What do computational predictors say about AKAP13 p.Arg367His (c.1100G>A)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

AKAP13 p.Arg367His

c.1100G>A · VCV4829879

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.015	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -3.8, phastCons 0.04
Regional constraint	o/e 1.14	unconstrained · MANE · 232 kb · p 1.5e-12 · regional, not allelic
Overall
CADD	6.244	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 0.0231% South Asian · 21/91,072 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00712% 115/1,614,146 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0231%	4,337
European (non-Finnish)	0.00712%	14,048
East Asian	0.00668%	14,959
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,008
Finnishnot grpmax-eligible	0.00156%	64,036
African / African-American	0.00133%	75,030

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: AKAP13
Protein: p.Arg367His
Coding: c.1100G>A
MANE Select: NM_007200
Type: single nucleotide variant
Location: chr15:85579168 (GRCh38)
Gene constraint: LOEUF 0.362 · pLI 1.00 (gnomAD)
Residue 367: the 'disordered' region

Full AKAP13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AKAP13 p.Ala2026= Benign/Likely benign ★★ same type
AKAP13 p.Arg2678Trp Benign ★★ same type
AKAP13 p.Glu1175= Benign/Likely benign ★★ same type
AKAP13 p.Glu334Lys Benign ★★ same type
AKAP13 p.Ile1260= Benign ★★ same type
AKAP13 p.Leu2461= Benign ★★ same type
AKAP13 p.Leu915= Benign ★★ same type
AKAP13 p.Lys410= 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/akap13-p-arg367his (accessed [today's date]).

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