Is AIRE p.Asp70fs (c.205_208dup) pathogenic?

AIRE p.Asp70fs (c.205208dup) is classified Pathogenic in AIRE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-17). Ultra-rare (popmax 0.0495%, mid); Associated with autoimmune polyendocrine syndrome type 1.

What condition is associated with AIRE p.Asp70fs (c.205_208dup)?

AIRE p.Asp70fs (c.205_208dup) is associated with autoimmune polyendocrine syndrome type 1 (ClinVar).

How common is AIRE p.Asp70fs (c.205_208dup) in the general population?

AIRE p.Asp70fs (c.205_208dup) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

How is Autoimmune polyendocrinopathy type 1 inherited?

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

AIRE p.Asp70fs

c.205_208dup · rs886041124 · VCV279674

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -2.1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.000205% 3/1,460,690 alleles · ultra-rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AIRE
Protein: p.Asp70fs
Coding: c.205_208dup
MANE Select: NM_000383
dbSNP: rs886041124
Type: Duplication
Location: chr21:44286628 (GRCh38)
Gene constraint: LOEUF 1.169 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.30 · 4 PDB
Residue 70: 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.Arg15delinsHisAlaGlyPheTer Pathogenic ★★ same condition
AIRE p.Gln173fs Pathogenic/Likely pathogenic ★★ same condition
AIRE p.Gly267fs Pathogenic/Likely pathogenic ★★ same condition
AIRE p.Leu175fs Pathogenic/Likely pathogenic ★★ same condition
AIRE p.Leu370fs Pathogenic ★★ same condition
AIRE p.Leu417fs Pathogenic ★★ same condition
AIRE p.Val436fs Likely pathogenic ★★ same condition
AIRE c.1095+23_1095+64dup Likely benign ★★ 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-asp70fs (accessed [today's date]).

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