IL6ST p.Pro222=
c.666C>T · rs200601494 · VCV1560434
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0139%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 7.918 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0139%
Admixed American · 8/57,362 alleles
Filtering AF
0.00688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00501%
Overall
0.000562%
9/1,602,306 alleles · ultra-rare
exomes 8/1,450,340 · genomes 1/151,966 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0139% | 7,170 |
| European (non-Finnish) | 8.51e-05% | 1,175,277 |
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
- IL6ST
- Protein
- p.Pro222=
- Coding
- c.666C>T
- MANE Select
- NM_002184
- dbSNP
- rs200601494
- Type
- single nucleotide variant
- Location
- chr5:55963499 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 20 PDB
- Residue 222
- an α-helix
Similar variants
- IL6ST p.Arg281Ter Pathogenic ★★ same type
- IL6ST c.1552+3A>C Uncertain significance ★★ same type
- IL6ST c.658+6T>G Uncertain significance ★★ same type
- IL6ST p.Ala11Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala174Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala278Gly Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala278Val Uncertain significance ★★ ⚠ same type
- IL6ST p.Ala517Pro 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/il6st-p-pro222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown