IFNAR1 p.Pro451=
c.1353G>A · rs371647017 · VCV1603755
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0414%, eas)
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 -7.7 | GERP -6.9 |
| Overall | ||
| CADD | 0.315 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0414%
East Asian · 18/43,430 alleles
Filtering AF
0.0268%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0221%
Overall
0.00303%
48/1,582,804 alleles · ultra-rare
exomes 48/1,430,662 · genomes 0/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0414% | 2,413 |
| Remaining individualsnot grpmax-eligible | 0.00326% | 30,683 |
| European (non-Finnish) | 0.00223% | 44,901 |
| Admixed American | 0.00192% | 52,092 |
| African / African-American | 0.00136% | 73,296 |
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
- IFNAR1
- Protein
- p.Pro451=
- Coding
- c.1353G>A
- MANE Select
- NM_000629
- dbSNP
- rs371647017
- Type
- single nucleotide variant
- Location
- chr21:33353696 (GRCh38)
- Gene constraint
- LOEUF 1.73 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.71 · 5 PDB
- Residue 451
- a UniProt-annotated variant site (in imd106; decreased protein abundance); a UniProt-annotated variant site (in imd106; no protein detected in homozygous patient cells; loss of type i interferon receptor activity); a UniProt-annotated variant site (in imd106; loss of localization at the plasma membrane; loss of type i interferon receptor activity)
Similar variants
- IFNAR1 c.377-2A>G Likely pathogenic ★★ same type
- IFNAR1 p.Tyr250Ter Pathogenic/Likely pathogenic ★★ same type
- IFNAR1 p.Ala17Val Uncertain significance ★★ ⚠ same type
- IFNAR1 p.Ala408Val Uncertain significance ★★ ⚠ same type
- IFNAR1 p.Arg124His Uncertain significance ★★ ⚠ same type
- IFNAR1 p.Arg306His Uncertain significance ★★ ⚠ same type
- IFNAR1 p.Arg340Gly Uncertain significance ★★ ⚠ same type
- IFNAR1 p.Asn44His 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/ifnar1-p-pro451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown