Is FOXP3 p.Arg397= (c.1191G>T) pathogenic?

FOXP3 p.Arg397= (c.1191G>T) is classified Likely benign in FOXP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-28). Very rare (popmax 0.00112%, nfe); Associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.

What condition is associated with FOXP3 p.Arg397= (c.1191G>T)?

FOXP3 p.Arg397= (c.1191G>T) is associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (ClinVar).

How common is FOXP3 p.Arg397= (c.1191G>T) in the general population?

FOXP3 p.Arg397= (c.1191G>T) is very rare (popmax 0.00112%, nfe) (gnomAD).

FOXP3 p.Arg397=

Q: How is Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome inherited?

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

c.1191G>T · rs141362642 · VCV2660530

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Conditions

immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome

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 -4.4	GERP -3.7
Overall
CADD	5.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% European (non-Finnish) · 10/895,329 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000826% 10/1,210,635 alleles · very rare exomes 9/1,098,201 · genomes 1/112,434 · joint denominator

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: FOXP3
Protein: p.Arg397=
Coding: c.1191G>T
MANE Select: NM_014009
dbSNP: rs141362642
Type: single nucleotide variant
Location: chrX:49251439 (GRCh38)
Structure: AlphaFold pLDDT 58.29 · 2 PDB
Residue 397: a UniProt-annotated variant site (in ipex); a DNA-binding region; a β-strand

Full FOXP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

FOXP3 p.Arg397Gln Pathogenic/Likely pathogenic ★★ same residue
FOXP3 p.Arg397Trp Pathogenic ★★ same residue
FOXP3 c.454+4A>G Likely pathogenic ★★ same condition
FOXP3 c.543-2A>G Likely pathogenic ★★ same condition
FOXP3 p.Ala384Thr Pathogenic/Likely pathogenic ★★ same condition
FOXP3 p.Ile363Val Pathogenic ★★ same condition
FOXP3 p.Pro339Ala Pathogenic/Likely pathogenic ★★ same condition
FOXP3 p.Val408Met 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/foxp3-p-arg397 (accessed [today's date]).

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