Is IRAK2 p.Ile5Val (c.13A>G) pathogenic?

IRAK2 p.Ile5Val (c.13A>G) is classified Uncertain significance in IRAK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.1357); Absent from gnomAD v4.1.

How common is IRAK2 p.Ile5Val (c.13A>G) in the general population?

IRAK2 p.Ile5Val (c.13A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IRAK2 p.Ile5Val (c.13A>G)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

IRAK2 p.Ile5Val

c.13A>G · rs1696655413 · VCV2311693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.08	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 77 kb · p 0.88 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IRAK2
Protein: p.Ile5Val
Coding: c.13A>G
MANE Select: NM_001570
dbSNP: rs1696655413
Type: single nucleotide variant
Location: chr3:10164967 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76 · 1 PDB
Residue 5: an α-helix

Full IRAK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IRAK2 p.Leu392Val Benign ★★ same type
IRAK2 p.Ala152Thr Uncertain significance ★ ⚠ same type
IRAK2 p.Ala192Thr Uncertain significance ★ ⚠ same type
IRAK2 p.Ala451Ser Uncertain significance ★ ⚠ same type
IRAK2 p.Ala477Thr Uncertain significance ★ ⚠ same type
IRAK2 p.Ala573Ser Uncertain significance ★ ⚠ same type
IRAK2 p.Ala601Val Uncertain significance ★ ⚠ same type
IRAK2 p.Arg312His Uncertain significance ★ 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/irak2-p-ile5val (accessed [today's date]).

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