Is STAT2 p.Leu599fs (c.1791del) pathogenic?

STAT2 p.Leu599fs (c.1791del) is classified Pathogenic in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). Very rare (popmax 8.47e-05%, nfe); Associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.

How common is STAT2 p.Leu599fs (c.1791del) in the general population?

STAT2 p.Leu599fs (c.1791del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

STAT2 p.Leu599fs

Q: What condition is associated with STAT2 p.Leu599fs (c.1791del)?

STAT2 p.Leu599fs (c.1791del) is associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (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.1791del · rs1877554115 · VCV966700

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.2e-05% 1/1,614,172 alleles · very rare exomes 1/1,461,892 · genomes 0/152,280 · joint denominator

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: STAT2
Protein: p.Leu599fs
Coding: c.1791del
MANE Select: NM_005419
dbSNP: rs1877554115
Type: Deletion
Location: chr12:56346889 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 599: the sh2 domain; a β-strand

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

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

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

STAT2 p.Leu599= Likely benign ★ same residue
STAT2 c.1209+1del Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Gln527fs Pathogenic ★ same condition
STAT2 p.Glu756fs Pathogenic ★ same condition
STAT2 p.Gly609fs Pathogenic ★ same condition
STAT2 p.Leu733fs Pathogenic ★ same condition
STAT2 p.Phe553fs Pathogenic ★ same condition
STAT2 p.Thr260fs 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/stat2-p-leu599fs (accessed [today's date]).

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