AIRE p.Arg538Ser
c.1612C>A · VCV4030095
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5158 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5158 | ambiguous |
|---|---|---|
| REVEL | 0.492 | indeterminate |
| SaProt | LLR -6.42 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.1 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 1.20 | unconstrained · MANE · 5,406 bp · p 0.00076 · regional, not allelic |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Arg538Ser
- Coding
- c.1612C>A
- MANE Select
- NM_000383
- Type
- single nucleotide variant
- Location
- chr21:44297701 (GRCh38)
- Gene constraint
- LOEUF 1.169 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.30 · 4 PDB
Similar variants
- AIRE p.Arg538Cys Uncertain significance ★★ ⚠ same residue
- AIRE p.Arg538Gly Uncertain significance ★ ⚠ same residue
- AIRE p.Arg538His Uncertain significance ★ ⚠ same residue
- AIRE p.Ala152Thr Uncertain significance ★★ ⚠ same condition
- AIRE p.Ala170Thr Uncertain significance ★★ ⚠ same condition
- AIRE p.Ala265Thr Uncertain significance ★★ ⚠ same condition
- AIRE p.Ala493Thr Uncertain significance ★★ ⚠ same condition
- AIRE p.Ala540Val Uncertain significance ★★ ⚠ 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-arg538ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown