Is IL1RN p.Pro132= (c.396C>G) pathogenic?

IL1RN p.Pro132= (c.396C>G) is classified Likely benign in IL1RN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-28). Absent from gnomAD v4.1; Associated with sterile multifocal osteomyelitis with periostitis and pustulosis.

What condition is associated with IL1RN p.Pro132= (c.396C>G)?

IL1RN p.Pro132= (c.396C>G) is associated with sterile multifocal osteomyelitis with periostitis and pustulosis (ClinVar).

How common is IL1RN p.Pro132= (c.396C>G) in the general population?

IL1RN p.Pro132= (c.396C>G) is absent from gnomAD v4.1 (gnomAD).

IL1RN p.Pro132=

Q: How is Sterile multifocal osteomyelitis with periostitis and pustulosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.396C>G · rs2466968900 · VCV2099783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

sterile multifocal osteomyelitis with periostitis and pustulosis

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 -0.94	GERP -3.5
Overall
CADD	2.649	PHRED · no single calibrated threshold — expert panels disagree

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: IL1RN
Protein: p.Pro132=
Coding: c.396C>G
MANE Select: NM_173842
dbSNP: rs2466968900
Type: single nucleotide variant
Location: chr2:113132733 (GRCh38)
Gene constraint: LOEUF 1.507 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 5 PDB

Full IL1RN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

sterile multifocal osteomyelitis with periostitis and pustulosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Sterile multifocal osteomyelitis with periostitis and pustulosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

IL1RN p.Pro132Leu Uncertain significance ★ ⚠ same residue
IL1RN p.Glu77Ter Pathogenic ★★ same condition
IL1RN p.Ser21= Likely pathogenic ★★ same condition
IL1RN c.*119C>T Uncertain significance ★★ same condition
IL1RN p.Ala140Thr Uncertain significance ★★ ⚠ same condition
IL1RN p.Ala2Thr Uncertain significance ★★ same condition
IL1RN p.Arg102Thr Uncertain significance ★★ ⚠ same condition
IL1RN p.Arg127Cys Uncertain significance ★★ ⚠ 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/il1rn-p-pro132 (accessed [today's date]).

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