AIRE p.Phe543fs
c.1626dup · VCV4856838
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -2.9, phastCons 0.49 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- AIRE
- Protein
- p.Phe543fs
- Coding
- c.1626dup
- MANE Select
- NM_000383
- Type
- Duplication
- Location
- chr21:44297710 (GRCh38)
- Gene constraint
- LOEUF 1.169 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.30 · 4 PDB
Similar variants
- AIRE p.Arg15delinsHisAlaGlyPheTer Pathogenic ★★ same type
- AIRE p.Asp70fs Pathogenic ★★ same type
- AIRE p.Gln173fs Pathogenic/Likely pathogenic ★★ same type
- AIRE p.Gly267fs Pathogenic/Likely pathogenic ★★ same type
- AIRE p.Leu175fs Pathogenic/Likely pathogenic ★★ same type
- AIRE p.Leu370fs Pathogenic ★★ same type
- AIRE p.Leu417fs Pathogenic ★★ same type
- AIRE p.Val436fs Likely pathogenic ★★ 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/aire-p-phe543fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown