Is AIRE p.Ala5fs (c.14_15del) pathogenic?

AIRE p.Ala5fs (c.1415del) is classified Pathogenic in AIRE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Absent from gnomAD; Associated with autoimmune polyendocrine syndrome type 1.

What condition is associated with AIRE p.Ala5fs (c.14_15del)?

AIRE p.Ala5fs (c.14_15del) is associated with autoimmune polyendocrine syndrome type 1 (ClinVar).

How common is AIRE p.Ala5fs (c.14_15del) in the general population?

AIRE p.Ala5fs (c.14_15del) is absent from gnomAD (gnomAD).

How is Autoimmune polyendocrinopathy type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AIRE p.Ala5fs

c.14_15del · rs2146375012 · VCV1458570

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autoimmune polyendocrine syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP 1.1, phastCons 0.66

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AIRE
Protein: p.Ala5fs
Coding: c.14_15del
MANE Select: NM_000383
dbSNP: rs2146375012
Type: Microsatellite
Location: chr21:44286018 (GRCh38)
Gene constraint: LOEUF 1.169 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.30 · 4 PDB
Residue 5: the hsr domain

Full AIRE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoimmune polyendocrine syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune polyendocrinopathy type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

AIRE p.Ala5Thr Uncertain significance ★★ ⚠ same residue
AIRE p.Ala5Leu Uncertain significance ★ same residue
AIRE p.Ala5= Likely benign ★ same residue
AIRE p.Arg494fs Pathogenic/Likely pathogenic ★★ same condition
AIRE p.Cys419fs Pathogenic ★ same condition
AIRE p.Val420fs Pathogenic ★ same condition
AIRE c.1095+2T>C Pathogenic/Likely pathogenic ★★ same condition
AIRE c.1096-1G>A 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-ala5fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown