Is STAT1 p.Lys286= (c.858A>G) pathogenic?

STAT1 p.Lys286= (c.858A>G) is classified Likely benign in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-16). Absent from gnomAD v4.1; Associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome.

What condition is associated with STAT1 p.Lys286= (c.858A>G)?

STAT1 p.Lys286= (c.858A>G) is associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, immunodeficiency 31B, Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (ClinVar).

How common is STAT1 p.Lys286= (c.858A>G) in the general population?

STAT1 p.Lys286= (c.858A>G) is absent from gnomAD v4.1 (gnomAD).

STAT1 p.Lys286=

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.858A>G · VCV3758856

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.7
Overall
CADD	1.348	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: STAT1
Protein: p.Lys286=
Coding: c.858A>G
MANE Select: NM_007315
Type: single nucleotide variant
Location: chr2:190995147 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 286: an α-helix; a UniProt-annotated variant site (in imd31c)

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

Also linked: immunodeficiency 31B Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

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

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

STAT1 p.Lys286Gln Likely pathogenic ★ ⚠ same residue
STAT1 p.Lys286Glu Uncertain significance ★ ⚠ same residue
STAT1 p.Lys286Ile Pathogenic same residue
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
STAT1 p.Asp171Asn 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-lys286 (accessed [today's date]).

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