Is STAT2 p.Gln274Ter (c.820C>T) pathogenic?

STAT2 p.Gln274Ter (c.820C>T) is classified Pathogenic/Likely pathogenic in STAT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-29). Absent from gnomAD v4.1; Associated with STAT2-related disorder.

What condition is associated with STAT2 p.Gln274Ter (c.820C>T)?

STAT2 p.Gln274Ter (c.820C>T) is associated with STAT2-related disorder, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (ClinVar).

How common is STAT2 p.Gln274Ter (c.820C>T) in the general population?

STAT2 p.Gln274Ter (c.820C>T) is absent from gnomAD v4.1 (gnomAD).

STAT2 p.Gln274Ter

c.820C>T · rs1878457865 · VCV1028887

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

STAT2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 24
Splicing
SpliceAI	Δ0.31	donor gain · deltas
Pangolin	Δ0.24	loss · gain 0.07 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 1.5, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: STAT2
Protein: p.Gln274Ter
Coding: c.820C>T
MANE Select: NM_005419
dbSNP: rs1878457865
Type: single nucleotide variant
Location: chr12:56351413 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 274: the 'mediates interaction with usp18' region; an α-helix

Full STAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

STAT2-related disorder

Also linked: primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Similar variants

STAT2 p.Arg667Ter Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Ala302Thr Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg300Cys Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg330Gln Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg409His Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg510Gln Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg544Gln Uncertain significance ★★ ⚠ 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/stat2-p-gln274ter (accessed [today's date]).

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