Is AIRE p.Pro401= (c.1203T>C) pathogenic?

AIRE p.Pro401= (c.1203T>C) is classified Benign in AIRE (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune polyendocrine syndrome type 1.

What condition is associated with AIRE p.Pro401= (c.1203T>C)?

AIRE p.Pro401= (c.1203T>C) is associated with autoimmune polyendocrine syndrome type 1 (ClinVar).

How is Autoimmune polyendocrinopathy type 1 inherited?

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

AIRE p.Pro401=

Q: How common is AIRE p.Pro401= (c.1203T>C) in the general population?

AIRE p.Pro401= (c.1203T>C) is common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1203T>C · rs61737072 · VCV35657

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 16%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autoimmune polyendocrine syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -2.8
Overall
CADD	0.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16% African / African-American · 12,022/74,928 alleles

Filtering AF 15.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.7%

Overall 0.856% 13,776/1,609,130 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16%	6
Admixed American	1.21%	83
Remaining individualsnot grpmax-eligible	1.13%	89
Middle Eastern	0.62%	161
European (non-Finnish)	0.0221%	4,516
South Asian	0.0221%	4,525
Finnishnot grpmax-eligible	0.0193%	5,188
East Asian	0.00447%	22,382

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.Pro401=
Coding: c.1203T>C
MANE Select: NM_000383
dbSNP: rs61737072
Type: single nucleotide variant
Location: chr21:44293100 (GRCh38)
Gene constraint: LOEUF 1.169 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.30 · 4 PDB

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.Pro401Arg Uncertain significance ★ ⚠ same residue
AIRE p.Pro401Thr Uncertain significance ★ ⚠ same residue
AIRE c.1095+2T>C Pathogenic/Likely pathogenic ★★ same condition
AIRE c.1096-1G>A Pathogenic ★★ same condition
AIRE c.1278+1G>A Likely pathogenic ★★ same condition
AIRE c.1279-2A>G Likely pathogenic ★★ same condition
AIRE c.1503+1G>A Likely pathogenic ★★ same condition
AIRE c.1503+1G>T Pathogenic/Likely 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-pro401 (accessed [today's date]).

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