Is FOXP3 p.Ser82= (c.246C>T) pathogenic?

FOXP3 p.Ser82= (c.246C>T) is classified Likely benign in FOXP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). Ultra-rare (popmax 0.0231%, mid); Associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.

What condition is associated with FOXP3 p.Ser82= (c.246C>T)?

FOXP3 p.Ser82= (c.246C>T) is associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (ClinVar).

How common is FOXP3 p.Ser82= (c.246C>T) in the general population?

FOXP3 p.Ser82= (c.246C>T) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

FOXP3 p.Ser82=

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.246C>T · rs368483472 · VCV1134751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.7	GERP -3.1
Overall
CADD	1.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% Middle Eastern · 1/4,324 alleles

Filtering AF 0.00279% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00246%

Overall 0.00332% 39/1,173,493 alleles · ultra-rare exomes 35/1,061,183 · genomes 4/112,310 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,324
European (non-Finnish)	0.00388%	25,760
East Asian	0.00315%	31,731
Remaining individualsnot grpmax-eligible	0.00216%	46,207
South Asian	0.00188%	53,062
African / African-American	0.00177%	56,470

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.Ser82=
Coding: c.246C>T
MANE Select: NM_014009
dbSNP: rs368483472
Type: single nucleotide variant
Location: chrX:49257733 (GRCh38)
Structure: AlphaFold pLDDT 58.29 · 2 PDB

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.Ser82Cys Uncertain significance ★ ⚠ 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.Arg397Gln Pathogenic/Likely pathogenic ★★ same condition
FOXP3 p.Arg397Trp Pathogenic ★★ same condition
FOXP3 p.Ile363Val Pathogenic ★★ same condition
FOXP3 p.Pro339Ala 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-ser82 (accessed [today's date]).

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