Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 32.9%, amr) — too common for a highly-penetrant pathogenic allele
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 -0.15 | GERP -2.1, phastCons 0.81 |
| Overall | ||
| CADD | 4.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32.9%
Admixed American · 18,820/57,282 alleles
Filtering AF
32.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 32.3%
Overall
28.8%
447,509/1,552,018 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 32.9% | 3 |
| Finnishnot grpmax-eligible | 31% | 3 |
| European (non-Finnish) | 30.2% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 28.6% | 4 |
| Remaining individualsnot grpmax-eligible | 28.1% | 4 |
| Middle Eastern | 25.2% | 4 |
| South Asian | 24.3% | 4 |
| Amishnot grpmax-eligible | 23.8% | 4 |
| African / African-American | 19.5% | 5 |
| East Asian | 12.8% | 8 |
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.Ser35=
- Coding
- c.105A>C
- MANE Select
- NM_001562
- dbSNP
- rs549908
- Type
- single nucleotide variant
- Location
- chr11:112150193 (GRCh38)
- Gene constraint
- LOEUF 1.867 · pLI 0.32 (gnomAD)
- Structure
- AlphaFold pLDDT 89.24 · 20 PDB
- Residue 35
- a β-strand
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-ser35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown