Is STAT1 p.Gln408= (c.1224A>G) pathogenic?

STAT1 p.Gln408= (c.1224A>G) is classified Uncertain significance in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Very rare (popmax 0.00167%, amr); Associated with Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.

What condition is associated with STAT1 p.Gln408= (c.1224A>G)?

STAT1 p.Gln408= (c.1224A>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.Gln408= (c.1224A>G) in the general population?

STAT1 p.Gln408= (c.1224A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

STAT1 p.Gln408=

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.1224A>G · rs549774353 · VCV2945760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.60	acceptor gain · deltas
Pangolin	Δ0.43	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 0.000124% 2/1,614,126 alleles · very rare exomes 1/1,461,808 · genomes 1/152,318 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
South Asian	0.0011%	91,084

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.Gln408=
Coding: c.1224A>G
MANE Select: NM_007315
dbSNP: rs549774353
Type: single nucleotide variant
Location: chr2:190985658 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 408: a β-strand

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.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-gln408 (accessed [today's date]).

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