IFNAR1 p.Ala449=
c.1347T>A · VCV3685749
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00273%, 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 -2.5 | GERP -3.8 |
| Overall | ||
| CADD | 0.595 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00273%
African / African-American · 2/73,270 alleles
Filtering AF
0.000453%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00017%
Overall
0.000126%
2/1,582,960 alleles · very rare
exomes 1/1,430,724 · genomes 1/152,236 · joint denominator
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.Ala449=
- Coding
- c.1347T>A
- MANE Select
- NM_000629
- Type
- single nucleotide variant
- Location
- chr21:33353690 (GRCh38)
- Gene constraint
- LOEUF 1.73 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.71 · 5 PDB
- Residue 449
- 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-ala449 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown