Is IRAK3 p.Ser288= (c.864G>T) pathogenic?

IRAK3 p.Ser288= (c.864G>T) is classified Likely benign in IRAK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-10). Very rare (popmax 0.00134%, afr); Associated with IRAK3-related disorder.

What condition is associated with IRAK3 p.Ser288= (c.864G>T)?

IRAK3 p.Ser288= (c.864G>T) is associated with IRAK3-related disorder (ClinVar).

How common is IRAK3 p.Ser288= (c.864G>T) in the general population?

IRAK3 p.Ser288= (c.864G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

IRAK3 p.Ser288=

c.864G>T · rs535521918 · VCV3049609

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

IRAK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.4
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,866 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,612,976 alleles · very rare exomes 3/1,460,852 · genomes 4/152,124 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,866
South Asian	0.0011%	91,062
European (non-Finnish)	0.000424%	235,818

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: IRAK3
Protein: p.Ser288=
Coding: c.864G>T
MANE Select: NM_007199
dbSNP: rs535521918
Type: single nucleotide variant
Location: chr12:66228347 (GRCh38)
Gene constraint: LOEUF 1.353 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 3 PDB
Residue 288: the protein kinase domain; a UniProt-annotated variant site (in)

Full IRAK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

IRAK3-related disorder

Similar variants

IRAK3 c.381+10G>A Likely benign same condition
IRAK3 p.Glu513= Likely benign same condition
IRAK3 p.Ile147Val Benign same condition
IRAK3 p.Ile171Val Likely benign same condition
IRAK3 p.Ile270Val Benign same condition
IRAK3 p.Leu400Val Likely benign same condition
IRAK3 p.Pro466Arg Benign same condition
IRAK3 p.Ser449= 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/irak3-p-ser288 (accessed [today's date]).

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