Is IL1RN p.Phe38= (c.114C>T) pathogenic?

IL1RN p.Phe38= (c.114C>T) is classified Likely benign in IL1RN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-02). Very rare (popmax 0.00271%, nfe); Associated with sterile multifocal osteomyelitis with periostitis and pustulosis.

What condition is associated with IL1RN p.Phe38= (c.114C>T)?

IL1RN p.Phe38= (c.114C>T) is associated with sterile multifocal osteomyelitis with periostitis and pustulosis (ClinVar).

How common is IL1RN p.Phe38= (c.114C>T) in the general population?

IL1RN p.Phe38= (c.114C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

IL1RN p.Phe38=

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.114C>T · rs139856782 · VCV2167241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

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 4	GERP 0.67, phastCons 1
Overall
CADD	19.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,852 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00198% 32/1,613,628 alleles · very rare exomes 32/1,461,392 · genomes 0/152,236 · joint denominator

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: IL1RN
Protein: p.Phe38=
Coding: c.114C>T
MANE Select: NM_173842
dbSNP: rs139856782
Type: single nucleotide variant
Location: chr2:113127738 (GRCh38)
Gene constraint: LOEUF 1.507 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.98 · 5 PDB
Residue 38: a β-strand

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.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
IL1RN p.Arg26Gln 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-phe38 (accessed [today's date]).

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