IL6ST p.Arg673=
c.2019G>A · rs373846785 · VCV2127485
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00271%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.156 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Pangolin | Δ0.22 | loss · gain 0.02 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 21.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
African / African-American · 2/73,774 alleles
Filtering AF
0.00045%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000168%
Overall
0.00032%
5/1,562,658 alleles · very rare
exomes 4/1,410,660 · genomes 1/151,998 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00271% | 36,887 |
| European (non-Finnish) | 0.000264% | 378,284 |
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.Arg673=
- Coding
- c.2019G>A
- MANE Select
- NM_002184
- dbSNP
- rs373846785
- Type
- single nucleotide variant
- Location
- chr5:55942670 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 20 PDB
- Residue 673
- the 'disordered' region; a UniProt-annotated variant site (in stws2; results in impaired cytokine-mediated signaling pathway with loss of response to il-6, il-11, il-27, osm and lif; does not localize to the cell membrane)
Similar variants
- IL6ST p.Arg673Gly Uncertain significance ★★ ⚠ same residue
- 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
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-arg673 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown