Is IL1RN p.Asp22= (c.66C>T) pathogenic?

IL1RN p.Asp22= (c.66C>T) is classified Conflicting classifications of pathogenicity in IL1RN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-10). Very rare (popmax 0.00144%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with IL1RN p.Asp22= (c.66C>T)?

IL1RN p.Asp22= (c.66C>T) is associated with autoinflammatory syndrome, sterile multifocal osteomyelitis with periostitis and pustulosis (ClinVar).

How common is IL1RN p.Asp22= (c.66C>T) in the general population?

IL1RN p.Asp22= (c.66C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

IL1RN p.Asp22=

c.66C>T · rs760885026 · VCV1107434

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Conditions

autoinflammatory syndrome

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 -0.33	GERP -1.4
Overall
CADD	0.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,178,688 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00105% 17/1,612,014 alleles · very rare exomes 16/1,460,480 · genomes 1/151,534 · 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.Asp22=
Coding: c.66C>T
MANE Select: NM_173842 · reported on NM_173841
dbSNP: rs760885026
Type: single nucleotide variant
Location: chr2:113120121 (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

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sterile multifocal osteomyelitis with periostitis and pustulosis

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-asp22 (accessed [today's date]).

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