Is STAT1 p.Asp257fs (c.770del) pathogenic?

STAT1 p.Asp257fs (c.770del) is classified Pathogenic in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). Associated with immunodeficiency 31B.

STAT1 p.Asp257fs

Q: What condition is associated with STAT1 p.Asp257fs (c.770del)?

STAT1 p.Asp257fs (c.770del) is associated with immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (ClinVar).

Q: How is Susceptibility to viral and mycobacterial infections due to STAT1 deficiency inherited?

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

c.770del · VCV3757694

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

immunodeficiency 31B

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 0.48	GERP -3.7, phastCons 0.87

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

Variant & gene context

Gene: STAT1
Protein: p.Asp257fs
Coding: c.770del
MANE Select: NM_007315
Type: Deletion
Location: chr2:190997871 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 257: an α-helix

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

Disease context

immunodeficiency 31B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

For Susceptibility to viral and mycobacterial infections due to STAT1 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

STAT1 p.Asp257= Likely benign ★ same residue
STAT1 p.Ile30fs Pathogenic ★★ same condition
STAT1 p.Val339fs Pathogenic ★★ same condition
STAT1 p.Glu411fs Pathogenic ★ same condition
STAT1 p.Ile232fs Pathogenic ★ same condition
STAT1 p.Ile612fs Pathogenic ★ same condition
STAT1 p.Leu667fs Pathogenic ★ same condition
STAT1 p.Lys361fs 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/stat1-p-asp257fs (accessed [today's date]).

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