Is IL18 p.Arg63Gln (c.188G>A) pathogenic?

IL18 p.Arg63Gln (c.188G>A) is classified Likely benign in IL18 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0743); Very rare (popmax 0.00443%, sas).

How common is IL18 p.Arg63Gln (c.188G>A) in the general population?

IL18 p.Arg63Gln (c.188G>A) is very rare (popmax 0.00443%, sas) (gnomAD).

What do computational predictors say about IL18 p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

IL18 p.Arg63Gln

c.188G>A · VCV4038245

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00443%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.002	strongly benign-leaning
SaProt	LLR -5.64	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 -3.2	GERP -3.9
Regional constraint	o/e 0.72	unconstrained · MANE · 11 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	0.032	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 0.00443% South Asian · 4/90,234 alleles

Filtering AF 0.00144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000897%

Overall 0.000745% 12/1,610,476 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00443%	22,558
Admixed American	0.00168%	59,348
Remaining individualsnot grpmax-eligible	0.0016%	62,370
African / African-American	0.00134%	74,776
European (non-Finnish)	0.000424%	235,710

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: IL18
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_001562
Type: single nucleotide variant
Location: chr11:112150110 (GRCh38)
Gene constraint: LOEUF 1.867 · pLI 0.32 (gnomAD)
Structure: AlphaFold pLDDT 89.24 · 20 PDB

Full IL18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IL18 p.Arg167Lys Uncertain significance ★ ⚠ same type
IL18 p.Asp36Asn Uncertain significance ★ ⚠ same type
IL18 p.Leu110Ile Uncertain significance ★ ⚠ same type
IL18 p.Met122Val Uncertain significance ★ ⚠ same type
IL18 p.Met149Thr Uncertain significance ★ ⚠ same type
IL18 p.Phe25Cys Uncertain significance ★ ⚠ same type
IL18 p.Phe66Cys Uncertain significance ★ ⚠ same type
IL18 c.80-5C>A Benign ★ 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/il18-p-arg63gln (accessed [today's date]).

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