Is IL36RN p.Pro117= (c.351G>A) pathogenic?

IL36RN p.Pro117= (c.351G>A) is classified Conflicting classifications of pathogenicity in IL36RN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0267%, eas); Associated with generalized pustular psoriasis.

What condition is associated with IL36RN p.Pro117= (c.351G>A)?

IL36RN p.Pro117= (c.351G>A) is associated with generalized pustular psoriasis (ClinVar).

How common is IL36RN p.Pro117= (c.351G>A) in the general population?

IL36RN p.Pro117= (c.351G>A) is ultra-rare (popmax 0.0267%, eas) (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.Pro117=

c.351G>A · rs202161658 · VCV1024624

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Conditions

generalized pustular psoriasis

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 -12	GERP -3.4
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,874 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00477% 77/1,613,936 alleles · ultra-rare exomes 69/1,461,718 · genomes 8/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
South Asian	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0048%	20,833
European (non-Finnish)	0.00407%	24,584
African / African-American	0.00133%	75,008

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.Pro117=
Coding: c.351G>A
MANE Select: NM_012275
dbSNP: rs202161658
Type: single nucleotide variant
Location: chr2:113062560 (GRCh38)
Gene constraint: LOEUF 1.311 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.62 · 4 PDB

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.Pro117Ala Uncertain significance ★★ ⚠ same residue
IL36RN p.Pro117Gln Uncertain significance ★ ⚠ same residue
IL36RN p.Pro117Leu 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

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-pro117 (accessed [today's date]).

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