USP18 p.Ser316=
c.948C>T · rs763731858 · VCV748037
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00696%, nfe)
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 -6.7 | |
| Overall | ||
| CADD | 0.444 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00696%
European (non-Finnish) · 82/1,178,088 alleles
Filtering AF
0.00572%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00526%
Overall
0.00546%
88/1,610,468 alleles · very rare
exomes 83/1,458,784 · genomes 5/151,684 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00696% | 14,367 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,176 |
| East Asian | 0.00223% | 44,802 |
| South Asian | 0.00221% | 45,326 |
| African / African-American | 0.00134% | 74,544 |
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
- USP18
- Protein
- p.Ser316=
- Coding
- c.948C>T
- MANE Select
- NM_017414
- dbSNP
- rs763731858
- Type
- single nucleotide variant
- Location
- chr22:18173206 (GRCh38)
- Gene constraint
- LOEUF 0.459 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 83.60 · 2 PDB
- Residue 316
- the usp domain; a UniProt-annotated variant site (in ptorch2); the 'mediates interaction with ifnar2' region
Similar variants
- USP18 p.Ser316Cys Uncertain significance ★ ⚠ same residue
- USP18 p.Ser2Asn Uncertain significance ★★ ⚠ same type
- USP18 p.Thr80Ile Uncertain significance ★★ ⚠ same type
- USP18 c.158-5T>G Benign/Likely benign ★★ same type
- USP18 p.Arg289Gln Likely benign ★★ same type
- USP18 p.Asn325Ser Benign/Likely benign ★★ same type
- USP18 p.Asp211= Benign/Likely benign ★★ same type
- USP18 p.Asp33Asn Likely 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/usp18-p-ser316 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown