Is AIRE p.Gln290fs (c.868del) pathogenic?

AIRE p.Gln290fs (c.868del) is classified Pathogenic/Likely pathogenic in AIRE (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-21). Absent from gnomAD v4.1; Associated with autoimmune polyendocrine syndrome type 1.

What condition is associated with AIRE p.Gln290fs (c.868del)?

AIRE p.Gln290fs (c.868del) is associated with autoimmune polyendocrine syndrome type 1 (ClinVar).

How common is AIRE p.Gln290fs (c.868del) in the general population?

AIRE p.Gln290fs (c.868del) is absent from gnomAD v4.1 (gnomAD).

How is Autoimmune polyendocrinopathy type 1 inherited?

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

AIRE p.Gln290fs

c.868del · rs2146379725 · VCV1359526

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,948)

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 7 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,610,948). 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.Gln290fs
Coding: c.868del
MANE Select: NM_000383
dbSNP: rs2146379725
Type: Deletion
Location: chr21:44290053 (GRCh38)
Gene constraint: LOEUF 1.169 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.30 · 4 PDB
Residue 290: the 'disordered' region

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.Gln290Ter Pathogenic/Likely pathogenic ★★ same residue
AIRE c.1203_1278+28del Likely pathogenic ★★ same condition
AIRE c.1278+1del Likely pathogenic ★★ same condition
AIRE p.Ala117fs Pathogenic ★★ same condition
AIRE p.Ala264fs Pathogenic ★★ same condition
AIRE p.Arg110fs Pathogenic ★★ same condition
AIRE p.Cys311fs Pathogenic ★★ same condition
AIRE p.Gln275fs 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-gln290fs (accessed [today's date]).

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