Is IL36G p.Cys61Phe (c.182G>T) pathogenic?

IL36G p.Cys61Phe (c.182G>T) is classified Uncertain significance in IL36G (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely pathogenic (0.7661); Ultra-rare (popmax 0.0267%, afr).

How common is IL36G p.Cys61Phe (c.182G>T) in the general population?

IL36G p.Cys61Phe (c.182G>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about IL36G p.Cys61Phe (c.182G>T)?

AlphaMissense predicts likely pathogenic (score 0.7661) — an in-silico prediction, not a clinical call.

IL36G p.Cys61Phe

c.182G>T · VCV3528823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7661 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7661	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -8.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 6,407 bp · p 0.78 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% African / African-American · 20/74,996 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00124% 20/1,613,572 alleles · ultra-rare exomes 6/1,461,274 · genomes 14/152,298 · 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: IL36G
Protein: p.Cys61Phe
Coding: c.182G>T
MANE Select: NM_019618
Type: single nucleotide variant
Location: chr2:112980030 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 91.25 · 6 PDB

Full IL36G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL36G p.Arg121Cys Uncertain significance ★ ⚠ same type
IL36G p.Arg13Thr Uncertain significance ★ ⚠ same type
IL36G p.Arg47Gln Uncertain significance ★ ⚠ same type
IL36G p.Asn31Thr Uncertain significance ★ ⚠ same type
IL36G p.Asp146Tyr Uncertain significance ★ ⚠ same type
IL36G p.Asp73Asn Uncertain significance ★ ⚠ same type
IL36G p.Asp7Gly Uncertain significance ★ ⚠ same type
IL36G p.Cys85Phe Uncertain significance ★ same type

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/il36g-p-cys61phe (accessed [today's date]).

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