Is STAT1 p.Gln299fs (c.895_896insT) pathogenic?

STAT1 p.Gln299fs (c.895896insT) is classified Pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). Associated with Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.

What condition is associated with STAT1 p.Gln299fs (c.895_896insT)?

STAT1 p.Gln299fs (c.895_896insT) is associated with Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency, immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (ClinVar).

STAT1 p.Gln299fs

Q: How is Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency inherited?

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

c.895_896insT · VCV4785831

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

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 10 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP -0.71, phastCons 1

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

Variant & gene context

Gene: STAT1
Protein: p.Gln299fs
Coding: c.895_896insT
MANE Select: NM_007315
Type: Insertion
Location: chr2:190995109 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 299: an α-helix

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

Disease context

Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 31B autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome

For Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

STAT1 p.Asn414Ter Pathogenic ★ same condition
STAT1 p.Gln299del Uncertain significance ★ same residue
STAT1 c.1098-12_1098-11insA Likely benign ★ same condition
STAT1 c.785+6_785+7insAC Likely benign ★ same condition
STAT1 p.Ala267Val Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gln Pathogenic ★★ ⚠ same condition
STAT1 p.Arg274Gly Pathogenic/Likely pathogenic ★★ same condition
STAT1 p.Arg274Trp 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/stat1-p-gln299fs (accessed [today's date]).

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