Is STAT1 p.Gln67Arg (c.200A>G) pathogenic?

STAT1 p.Gln67Arg (c.200A>G) is classified Conflicting classifications of pathogenicity in STAT1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-18). AlphaMissense: likely pathogenic (0.729); Absent from gnomAD v4.1; Associated with STAT1-related disorder.

How common is STAT1 p.Gln67Arg (c.200A>G) in the general population?

STAT1 p.Gln67Arg (c.200A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT1 p.Gln67Arg (c.200A>G)?

AlphaMissense predicts likely pathogenic (score 0.729) — an in-silico prediction, not a clinical call.

STAT1 p.Gln67Arg

Q: What condition is associated with STAT1 p.Gln67Arg (c.200A>G)?

STAT1 p.Gln67Arg (c.200A>G) is associated with STAT1-related disorder, immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome (ClinVar).

c.200A>G · rs2470565369 · VCV2120366

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.729 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

STAT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.729	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -10.71	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 2,434 bp · p 7.1e-17 · regional, not allelic
Overall
CADD	26.0	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

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.Gln67Arg
Coding: c.200A>G
MANE Select: NM_007315
dbSNP: rs2470565369
Type: single nucleotide variant
Location: chr2:191009036 (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

STAT1-related disorder

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.Gln67Pro Pathogenic ★ same residue
STAT1 p.Gln67= 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-gln67arg (accessed [today's date]).

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