Is STAT2 p.Arg345Lys (c.1034G>A) pathogenic?

STAT2 p.Arg345Lys (c.1034G>A) is classified Uncertain significance in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: ambiguous (0.4478); Absent from gnomAD v4.1; Associated with pseudo-TORCH syndrome 3.

What condition is associated with STAT2 p.Arg345Lys (c.1034G>A)?

STAT2 p.Arg345Lys (c.1034G>A) is associated with pseudo-TORCH syndrome 3 (ClinVar).

How common is STAT2 p.Arg345Lys (c.1034G>A) in the general population?

STAT2 p.Arg345Lys (c.1034G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT2 p.Arg345Lys (c.1034G>A)?

AlphaMissense predicts ambiguous (score 0.4478) — an in-silico prediction, not a clinical call.

STAT2 p.Arg345Lys

c.1034G>A · rs2547256124 · VCV2671942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

pseudo-TORCH syndrome 3

Computational evidence

Protein change
AlphaMissense	0.4478	ambiguous
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -8.41	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.54	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.70	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	34.0	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: STAT2
Protein: p.Arg345Lys
Coding: c.1034G>A
MANE Select: NM_005419
dbSNP: rs2547256124
Type: single nucleotide variant
Location: chr12:56351098 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 345: the 'mediates interaction with usp18' region; the 'interaction with heartland virus nss' region; the 'interaction with sftsv virus nss' region; a β-strand

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

Disease context

pseudo-TORCH syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STAT2 p.Arg667Gln Uncertain significance ★★ ⚠ same condition
STAT2 p.Ser12Gly Uncertain significance ★★ ⚠ same condition
STAT2 p.Arg148Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
STAT2 p.Arg374Gln Uncertain significance ★ ⚠ same condition
STAT2 p.Arg148Trp Pathogenic ⚠ same condition
STAT2 p.Arg667Ter Pathogenic/Likely pathogenic ★★ same type
STAT2 p.Gln274Ter Pathogenic/Likely pathogenic ★★ same type
STAT2 p.Ala219Thr Uncertain significance ★★ ⚠ same type

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-arg345lys (accessed [today's date]).

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