Is STAT1 p.His45= (c.135C>T) pathogenic?

STAT1 p.His45= (c.135C>T) is classified Likely benign in STAT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-22). Very rare (popmax 0.00669%, eas); Associated with autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome.

What condition is associated with STAT1 p.His45= (c.135C>T)?

STAT1 p.His45= (c.135C>T) 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.His45= (c.135C>T) in the general population?

STAT1 p.His45= (c.135C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

STAT1 p.His45=

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.135C>T · rs566696388 · VCV1574946

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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 -2.1	GERP -3.5
Overall
CADD	6.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,866 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00397% 64/1,614,016 alleles · very rare exomes 60/1,461,716 · genomes 4/152,300 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00424%	23,599
African / African-American	0.004%	25,012
South Asian	0.00329%	30,357
Admixed American	0.00167%	60,020

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.His45=
Coding: c.135C>T
MANE Select: NM_007315
dbSNP: rs566696388
Type: single nucleotide variant
Location: chr2:191009101 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 45: 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

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.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
STAT1 p.Asp292Glu Likely pathogenic ★★ ⚠ same condition
STAT1 p.Cys324Arg Likely pathogenic ★★ same condition
STAT1 p.Gln271Pro 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/stat1-p-his45 (accessed [today's date]).

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