AIRE p.Arg473=
c.1417A>C · rs2146385780 · VCV1554468
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
autoimmune polyendocrine syndrome type 1
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 1.2, phastCons 0.96 |
| Overall | ||
| CADD | 3.829 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AIRE
- Protein
- p.Arg473=
- Coding
- c.1417A>C
- MANE Select
- NM_000383
- dbSNP
- rs2146385780
- Type
- single nucleotide variant
- Location
- chr21:44294417 (GRCh38)
- Gene constraint
- LOEUF 1.169 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.30 · 4 PDB
- Residue 473
- a turn
Disease context
autoimmune polyendocrine syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Autoimmune polyendocrinopathy type 1 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Childhood
- Prevalence
- 1-9 / 100 000 (Finland)
Similar variants
- AIRE p.Arg473Lys Uncertain significance ★ ⚠ same residue
- AIRE p.Arg473Thr Uncertain significance ★ ⚠ same residue
- AIRE c.1095+2T>C Pathogenic/Likely pathogenic ★★ same condition
- AIRE c.1096-1G>A Pathogenic ★★ same condition
- AIRE c.1278+1G>A Likely pathogenic ★★ same condition
- AIRE c.1279-2A>G Likely pathogenic ★★ same condition
- AIRE c.1503+1G>A Likely pathogenic ★★ same condition
- AIRE c.1503+1G>T Pathogenic/Likely pathogenic ★★ same condition
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/aire-p-arg473 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown