Is STAT1 p.Ile232fs (c.693_696del) pathogenic?

STAT1 p.Ile232fs (c.693696del) is classified Pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). Very rare (popmax 0.0011%, sas); Associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome.

How common is STAT1 p.Ile232fs (c.693_696del) in the general population?

STAT1 p.Ile232fs (c.693_696del) is very rare (popmax 0.0011%, sas) (gnomAD).

STAT1 p.Ile232fs

Q: What condition is associated with STAT1 p.Ile232fs (c.693_696del)?

STAT1 p.Ile232fs (c.693_696del) is associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (ClinVar).

Q: How is STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome inherited?

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

c.693_696del · VCV3384050

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 9 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -0.47, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.19e-05% 1/1,614,252 alleles · very rare exomes 1/1,461,890 · genomes 0/152,362 · 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: STAT1
Protein: p.Ile232fs
Coding: c.693_696del
MANE Select: NM_007315
Type: Deletion
Location: chr2:190997945 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 232: an α-helix

Full STAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

STAT1 p.Val339fs Pathogenic ★★ same condition
STAT1 p.Asp257fs Pathogenic ★ same condition
STAT1 p.Glu411fs Pathogenic ★ same condition
STAT1 p.Ile612fs Pathogenic ★ same condition
STAT1 p.Leu667fs Pathogenic ★ same condition
STAT1 p.Lys361fs Likely pathogenic ★ same condition
STAT1 c.1632+6del Uncertain significance ★ same condition
STAT1 c.2059+6_2059+7del Uncertain significance ★ 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/stat1-p-ile232fs (accessed [today's date]).

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