Is STAT2 p.Pro709= (c.2127G>A) pathogenic?

STAT2 p.Pro709= (c.2127G>A) is classified Likely benign in STAT2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-11). Ultra-rare (popmax 0.0626%, sas); Associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.

How common is STAT2 p.Pro709= (c.2127G>A) in the general population?

STAT2 p.Pro709= (c.2127G>A) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

STAT2 p.Pro709=

Q: What condition is associated with STAT2 p.Pro709= (c.2127G>A)?

STAT2 p.Pro709= (c.2127G>A) 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.2127G>A · rs140174092 · VCV769390

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.5	GERP -3.4
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% South Asian · 54/86,230 alleles

Filtering AF 0.0492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0445%

Overall 0.00666% 104/1,562,204 alleles · ultra-rare exomes 91/1,409,990 · genomes 13/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,597
Middle Eastern	0.0499%	2,005
African / African-American	0.0136%	7,344
Remaining individualsnot grpmax-eligible	0.00496%	20,171
Admixed American	0.00387%	25,868
European (non-Finnish)	0.00278%	35,996

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.Pro709=
Coding: c.2127G>A
MANE Select: NM_005419
dbSNP: rs140174092
Type: single nucleotide variant
Location: chr12:56344111 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB

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.Pro709Leu Uncertain significance ★ ⚠ same residue
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

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-pro709 (accessed [today's date]).

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