Is IL36RN p.Pro137= (c.411C>T) pathogenic?

IL36RN p.Pro137= (c.411C>T) is classified Likely benign in IL36RN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). Ultra-rare (popmax 0.02%, amr); Associated with generalized pustular psoriasis.

What condition is associated with IL36RN p.Pro137= (c.411C>T)?

IL36RN p.Pro137= (c.411C>T) is associated with generalized pustular psoriasis (ClinVar).

How common is IL36RN p.Pro137= (c.411C>T) in the general population?

IL36RN p.Pro137= (c.411C>T) is ultra-rare (popmax 0.02%, amr) (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.Pro137=

c.411C>T · rs765211863 · VCV529890

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

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 -11	GERP -3.1
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,004 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000992% 16/1,613,324 alleles · ultra-rare exomes 14/1,461,176 · genomes 2/152,148 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,000
East Asian	0.00446%	22,440
South Asian	0.0022%	45,541

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.Pro137=
Coding: c.411C>T
MANE Select: NM_012275
dbSNP: rs765211863
Type: single nucleotide variant
Location: chr2:113062620 (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 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
IL36RN p.Arg10Gln Uncertain significance ★★ ⚠ same condition
IL36RN p.Glu112Lys 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-pro137 (accessed [today's date]).

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