IFNAR2 p.Ser123=
c.369A>G · rs139177032 · VCV1453685
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.044%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.61 | GERP 1.5 |
| Overall | ||
| CADD | 0.881 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.044%
African / African-American · 33/74,942 alleles
Filtering AF
0.0322%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0281%
Overall
0.00235%
38/1,614,050 alleles · ultra-rare
exomes 19/1,461,820 · genomes 19/152,230 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.044% | 2,271 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
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.Ser123=
- Coding
- c.369A>G
- MANE Select
- NM_001289125
- dbSNP
- rs139177032
- Type
- single nucleotide variant
- Location
- chr21:33246865 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.86 · 9 PDB
- Residue 123
- 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-ser123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown