IL6ST p.Phe613=
c.1839T>C · rs762546075 · VCV1926089
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 2.6 | GERP -0.73, phastCons 1 |
| Overall | ||
| CADD | 11.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,832 alleles
Filtering AF
0.00178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000892%
Overall
0.000249%
4/1,606,592 alleles · very rare
exomes 3/1,454,354 · genomes 1/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00669% | 14,944 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,258 |
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.Phe613=
- Coding
- c.1839T>C
- MANE Select
- NM_002184
- dbSNP
- rs762546075
- Type
- single nucleotide variant
- Location
- chr5:55951465 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.94 · 20 PDB
- Residue 613
- the fibronectin type-iii 5 domain; 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.Phe613fs Pathogenic ★ 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-phe613 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown