Is IRAK1 p.Arg366= (c.1098C>T) pathogenic?

IRAK1 p.Arg366= (c.1098C>T) is classified Likely benign in IRAK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-11). Rare (popmax 0.215%, afr); Associated with IRAK1-related disorder.

What condition is associated with IRAK1 p.Arg366= (c.1098C>T)?

IRAK1 p.Arg366= (c.1098C>T) is associated with IRAK1-related disorder (ClinVar).

How common is IRAK1 p.Arg366= (c.1098C>T) in the general population?

IRAK1 p.Arg366= (c.1098C>T) is rare (popmax 0.215%, afr) (gnomAD).

IRAK1 p.Arg366=

c.1098C>T · rs149520139 · VCV3040466

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.215%, afr)

Conditions

IRAK1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.038	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -0.86, phastCons 1
Overall
CADD	5.936	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.215% African / African-American · 124/57,717 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.0107% 130/1,211,271 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.215%	465
Remaining individualsnot grpmax-eligible	0.0084%	11,902
Admixed American	0.00434%	23,036

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: IRAK1
Protein: p.Arg366=
Coding: c.1098C>T
MANE Select: NM_001569
dbSNP: rs149520139
Type: single nucleotide variant
Location: chrX:154016575 (GRCh38)
Structure: AlphaFold pLDDT 70.27 · 1 PDB
Residue 366: the protein kinase domain

Full IRAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IRAK1-related disorder

Similar variants

IRAK1 p.Arg366Cys Likely benign ★ same residue
IRAK1 p.Gly399Arg Uncertain significance same condition
IRAK1 p.Trp130Cys Uncertain significance ⚠ same condition
IRAK1 c.137-8C>A Likely benign same condition
IRAK1 c.729+10G>A Likely benign same condition
IRAK1 c.909+9A>G Likely benign same condition
IRAK1 p.Lys242= Likely benign same condition
IRAK1 p.Ser213= Likely benign same condition

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/irak1-p-arg366 (accessed [today's date]).

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