IFNAR2 p.Ser223=
c.669T>G · rs371115590 · VCV1534548
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0506%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.17 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.8, phastCons 0.001 |
| Overall | ||
| CADD | 4.34 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0506%
African / African-American · 38/75,054 alleles
Filtering AF
0.0379%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0334%
Overall
0.00316%
51/1,614,018 alleles · ultra-rare
exomes 24/1,461,670 · genomes 27/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0506% | 1,975 |
| Middle Eastern | 0.0165% | 6,058 |
| Admixed American | 0.00833% | 12,003 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.000339% | 294,977 |
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.Ser223=
- Coding
- c.669T>G
- MANE Select
- NM_001289125
- dbSNP
- rs371115590
- Type
- single nucleotide variant
- Location
- chr21:33252790 (GRCh38)
- Gene constraint
- LOEUF 0.761 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.86 · 9 PDB
- Residue 223
- an α-helix
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-ser223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown