Is IL36RN p.Ala92Val (c.275C>T) pathogenic?

IL36RN p.Ala92Val (c.275C>T) is classified Uncertain significance in IL36RN (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-21). AlphaMissense: likely benign (0.0812); Absent from gnomAD v4.1; Associated with generalized pustular psoriasis.

What condition is associated with IL36RN p.Ala92Val (c.275C>T)?

IL36RN p.Ala92Val (c.275C>T) is associated with generalized pustular psoriasis (ClinVar).

How common is IL36RN p.Ala92Val (c.275C>T) in the general population?

IL36RN p.Ala92Val (c.275C>T) is absent from gnomAD v4.1 (gnomAD).

How is Generalized pustular psoriasis inherited?

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

What do computational predictors say about IL36RN p.Ala92Val (c.275C>T)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

IL36RN p.Ala92Val

c.275C>T · rs1685662918 · VCV837544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

generalized pustular psoriasis

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 3,235 bp · p 0.98 · regional, not allelic
Overall
CADD	15.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IL36RN
Protein: p.Ala92Val
Coding: c.275C>T
MANE Select: NM_012275
dbSNP: rs1685662918
Type: single nucleotide variant
Location: chr2:113062484 (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.Ala92fs Pathogenic ★ 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
IL36RN p.Arg10Gln 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-ala92val (accessed [today's date]).

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