Is STAT2 p.Glu654del (c.1957GAG[1]) pathogenic?

STAT2 p.Glu654del (c.1957GAG[1]) is classified Uncertain significance in STAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). Very rare (popmax 0.00333%, amr); Associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.

What condition is associated with STAT2 p.Glu654del (c.1957GAG[1])?

STAT2 p.Glu654del (c.1957GAG[1]) is associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection (ClinVar).

How common is STAT2 p.Glu654del (c.1957GAG[1]) in the general population?

STAT2 p.Glu654del (c.1957GAG[1]) is very rare (popmax 0.00333%, amr) (gnomAD).

STAT2 p.Glu654del

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.1957GAG[1] · rs775996290 · VCV577456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,020 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,614,132 alleles · very rare exomes 5/1,461,894 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,010
Remaining individualsnot grpmax-eligible	0.0016%	62,508
European (non-Finnish)	0.000169%	590,016

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.Glu654del
Coding: c.1957GAG[1]
MANE Select: NM_005419
dbSNP: rs775996290
Type: Microsatellite
Location: chr12:56346524 (GRCh38)
Gene constraint: LOEUF 0.497 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 78.45 · 6 PDB
Residue 654: the sh2 domain

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.Leu536del Uncertain significance ★ same condition
STAT2 p.Ser506del Uncertain significance ★ same condition
STAT2 c.1116-10_1116-8del Likely benign ★ same condition
STAT2 c.1257+16_1257+17del Likely benign ★ same condition
STAT2 c.2045-20_2045-18del Likely benign ★ same condition
STAT2 c.548-26GACT[3] Likely benign ★ same condition
STAT2 c.1209+1del Pathogenic/Likely pathogenic ★★ same condition
STAT2 p.Arg667Ter Pathogenic/Likely 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-glu654del (accessed [today's date]).

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