IL12RB1 p.Asp487=
c.1461T>C · rs542734526 · VCV328580
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 -7 | GERP -2.6 |
| Overall | ||
| CADD | 0.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0812% | 1,231 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,616 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,596 |
| African / African-American | 0.00133% | 75,030 |
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
- IL12RB1
- Protein
- p.Asp487=
- Coding
- c.1461T>C
- MANE Select
- NM_005535
- dbSNP
- rs542734526
- Type
- single nucleotide variant
- Location
- chr19:18066564 (GRCh38)
- Gene constraint
- LOEUF 0.862 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.84 · 7 PDB
- Residue 487
- a β-strand; the fibronectin type-iii 5 domain
Disease context
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
Similar variants
- IL12RB1 p.Asp487Glu Likely benign ★★ same residue
- IL12RB1 p.Asp487Asn Uncertain significance ★ ⚠ same residue
- IL12RB1 c.1791+2T>G Pathogenic ★★ same condition
- IL12RB1 c.64+2T>G Pathogenic ★★ same condition
- IL12RB1 p.Arg173Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- IL12RB1 p.Arg211Pro Pathogenic ★★ same condition
- IL12RB1 p.Arg283Ter Pathogenic ★★ same condition
- IL12RB1 p.Arg486Ter Pathogenic ★★ same condition
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/il12rb1-p-asp487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown