Is FOXP3 p.Ser319= (c.957C>T) pathogenic?

FOXP3 p.Ser319= (c.957C>T) is classified Likely benign in FOXP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Absent from gnomAD v4.1; Associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome.

What condition is associated with FOXP3 p.Ser319= (c.957C>T)?

FOXP3 p.Ser319= (c.957C>T) is associated with immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (ClinVar).

How common is FOXP3 p.Ser319= (c.957C>T) in the general population?

FOXP3 p.Ser319= (c.957C>T) is absent from gnomAD v4.1 (gnomAD).

FOXP3 p.Ser319=

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.957C>T · VCV4736278

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.41	GERP -3.1, phastCons 0.97
Overall
CADD	7.569	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FOXP3
Protein: p.Ser319=
Coding: c.957C>T
MANE Select: NM_014009
Type: single nucleotide variant
Location: chrX:49253927 (GRCh38)
Structure: AlphaFold pLDDT 58.29 · 2 PDB
Residue 319: the 'interaction with runx1' region

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 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
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-ser319 (accessed [today's date]).

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