IFNAR2 p.Leu56=
c.166T>C · rs36088527 · VCV2974810
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
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 -0.49 | GERP 5, phastCons 0.025 |
| Overall | ||
| CADD | 7.106 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,996 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.000931%
15/1,611,422 alleles · ultra-rare
exomes 8/1,459,102 · genomes 7/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,818 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,797 |
| European (non-Finnish) | 8.49e-05% | 1,177,540 |
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
- IFNAR2
- Protein
- p.Leu56=
- Coding
- c.166T>C
- MANE Select
- NM_001289125
- dbSNP
- rs36088527
- Type
- single nucleotide variant
- Location
- chr21:33245019 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.86 · 9 PDB
Similar variants
- IFNAR2 c.840+1G>T Uncertain significance ★★ same type
- IFNAR2 p.Arg397Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Arg90Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asn146Ser Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asn281Tyr Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asp198Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Asp437Gly Uncertain significance ★★ ⚠ same type
- IFNAR2 p.Glu184Lys 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/ifnar2-p-leu56 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown