IFNAR2 p.Glu138=
c.414G>A · rs778037937 · VCV1669471
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0278%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.027 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.34 | GERP -6.7, phastCons 0.011 |
| Overall | ||
| CADD | 3.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0278%
South Asian · 25/89,946 alleles
Filtering AF
0.0193%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0165%
Overall
0.00162%
26/1,608,780 alleles · ultra-rare
exomes 25/1,456,562 · genomes 1/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0278% | 3,598 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,244 |
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.Glu138=
- Coding
- c.414G>A
- MANE Select
- NM_001289125
- dbSNP
- rs778037937
- Type
- single nucleotide variant
- Location
- chr21:33248728 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.86 · 9 PDB
- Residue 138
- a UniProt-annotated variant site (no effect on activation of stat1 upon ifna2 or ifng binding); a β-strand
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-glu138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown