Is STAT1 p.Arg241Gln (c.722G>A) pathogenic?

STAT1 p.Arg241Gln (c.722G>A) is classified Conflicting classifications of pathogenicity in STAT1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0686); Rare (popmax 0.142%, amr); Associated with Inborn genetic diseases.

How common is STAT1 p.Arg241Gln (c.722G>A) in the general population?

STAT1 p.Arg241Gln (c.722G>A) is rare (popmax 0.142%, amr) (gnomAD).

What do computational predictors say about STAT1 p.Arg241Gln (c.722G>A)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

STAT1 p.Arg241Gln

Q: What condition is associated with STAT1 p.Arg241Gln (c.722G>A)?

STAT1 p.Arg241Gln (c.722G>A) is associated with Inborn genetic diseases, immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (ClinVar).

c.722G>A · rs146273341 · VCV333286

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.142%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -9.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.22	GERP -2.3
Regional constraint	o/e 0.42	unconstrained · MANE · 5,939 bp · p 3.1e-13 · regional, not allelic
Overall
CADD	11.93	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% Admixed American · 85/60,030 alleles

Filtering AF 0.117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.108%

Overall 0.0194% 313/1,614,218 alleles · rare exomes 251/1,461,886 · genomes 62/152,332 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.142%	706
Remaining individualsnot grpmax-eligible	0.0352%	2,841
African / African-American	0.0293%	3,411
European (non-Finnish)	0.0155%	6,448
East Asian	0.00223%	44,890

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.Arg241Gln
Coding: c.722G>A
MANE Select: NM_007315
dbSNP: rs146273341
Type: single nucleotide variant
Location: chr2:190997919 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 241: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 31B autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

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-arg241gln (accessed [today's date]).

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