Is IL36RN p.Arg102= (c.306G>A) pathogenic?

IL36RN p.Arg102= (c.306G>A) is classified Likely benign in IL36RN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). Ultra-rare (popmax 0.0164%, mid); Associated with generalized pustular psoriasis.

What condition is associated with IL36RN p.Arg102= (c.306G>A)?

IL36RN p.Arg102= (c.306G>A) is associated with generalized pustular psoriasis (ClinVar).

How common is IL36RN p.Arg102= (c.306G>A) in the general population?

IL36RN p.Arg102= (c.306G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Generalized pustular psoriasis inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

IL36RN p.Arg102=

c.306G>A · rs143557954 · VCV757065

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

generalized pustular psoriasis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.46	GERP -2.9, phastCons 0.019
Overall
CADD	4.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00551% 89/1,613,986 alleles · ultra-rare exomes 83/1,461,846 · genomes 6/152,140 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00695%	14,391
Finnishnot grpmax-eligible	0.00156%	63,984

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: IL36RN
Protein: p.Arg102=
Coding: c.306G>A
MANE Select: NM_012275
dbSNP: rs143557954
Type: single nucleotide variant
Location: chr2:113062515 (GRCh38)
Gene constraint: LOEUF 1.311 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.62 · 4 PDB
Residue 102: a β-strand

Full IL36RN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

generalized pustular psoriasis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Generalized pustular psoriasis (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: Adult
Prevalence: 1-9 / 1 000 000 (France)

Similar variants

IL36RN p.Arg102Gln Uncertain significance ★ ⚠ same residue
IL36RN p.Arg102Trp Uncertain significance ★★ same residue
IL36RN c.115+6T>C Pathogenic/Likely pathogenic ★★ same condition
IL36RN p.Leu27Pro Pathogenic ★★ same condition
IL36RN c.115+5G>A Uncertain significance ★★ same condition
IL36RN c.244-5G>A Uncertain significance ★★ same condition
IL36RN c.*401A>C Uncertain significance ★★ same condition
IL36RN p.Arg103Gln 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/il36rn-p-arg102 (accessed [today's date]).

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