Is STAT2 p.Ser12Gly (c.34A>G) pathogenic?

STAT2 p.Ser12Gly (c.34A>G) is classified Uncertain significance in STAT2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-06-24). AlphaMissense: likely benign (0.0672); Absent from gnomAD v4.1; Associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.

How common is STAT2 p.Ser12Gly (c.34A>G) in the general population?

STAT2 p.Ser12Gly (c.34A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT2 p.Ser12Gly (c.34A>G)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

STAT2 p.Ser12Gly

Q: What condition is associated with STAT2 p.Ser12Gly (c.34A>G)?

STAT2 p.Ser12Gly (c.34A>G) is associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, pseudo-TORCH syndrome 3 (ClinVar).

Q: How is Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.34A>G · rs1565660719 · VCV626024

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.03	GERP -3.3
Regional constraint	o/e 0.73	unconstrained · MANE · 13 kb · p 6.2e-18 · regional, not allelic
Overall
CADD	12.92	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser12Gly
Coding: c.34A>G
MANE Select: NM_005419
dbSNP: rs1565660719
Type: single nucleotide variant
Location: chr12:56356538 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 12: an α-helix

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

Disease context

primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pseudo-TORCH syndrome 3

For Primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

STAT2 p.Arg667Ter Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Gln274Ter 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

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-ser12gly (accessed [today's date]).

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