Is STAT1 p.Gln67= (c.201A>G) pathogenic?

STAT1 p.Gln67= (c.201A>G) is classified Conflicting classifications of pathogenicity in STAT1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-18). Very rare (popmax 0.00801%, afr); Associated with Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.

What condition is associated with STAT1 p.Gln67= (c.201A>G)?

STAT1 p.Gln67= (c.201A>G) 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).

How common is STAT1 p.Gln67= (c.201A>G) in the general population?

STAT1 p.Gln67= (c.201A>G) is very rare (popmax 0.00801%, afr) (gnomAD).

STAT1 p.Gln67=

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.201A>G · rs148148052 · VCV712811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -3.5
Overall
CADD	4.573	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,936 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00273% 44/1,613,992 alleles · very rare exomes 40/1,461,772 · genomes 4/152,220 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
European (non-Finnish)	0.00305%	32,777
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Gln67=
Coding: c.201A>G
MANE Select: NM_007315
dbSNP: rs148148052
Type: single nucleotide variant
Location: chr2:191009035 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 67: 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.Gln67Pro Pathogenic ★ same residue
STAT1 p.Gln67Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
STAT1 p.Gln67Lys Uncertain significance ★ ⚠ 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-gln67 (accessed [today's date]).

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