Is STAT2 p.Leu718= (c.2152C>T) pathogenic?

STAT2 p.Leu718= (c.2152C>T) is classified Likely benign in STAT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-12). Ultra-rare (popmax 0.0917%, sas); Associated with primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection.

How common is STAT2 p.Leu718= (c.2152C>T) in the general population?

STAT2 p.Leu718= (c.2152C>T) is ultra-rare (popmax 0.0917%, sas) (gnomAD).

STAT2 p.Leu718=

Q: What condition is associated with STAT2 p.Leu718= (c.2152C>T)?

STAT2 p.Leu718= (c.2152C>T) 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.2152C>T · rs750452354 · VCV1594437

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0917%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -0.59, phastCons 0.033
Overall
CADD	1.866	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0917% South Asian · 81/88,334 alleles

Filtering AF 0.0756% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0696%

Overall 0.00537% 85/1,583,432 alleles · ultra-rare exomes 83/1,431,234 · genomes 2/152,198 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0917%	1,091
African / African-American	0.0027%	37,094
Remaining individualsnot grpmax-eligible	0.00163%	61,404
European (non-Finnish)	8.59e-05%	1,163,524

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.Leu718=
Coding: c.2152C>T
MANE Select: NM_005419
dbSNP: rs750452354
Type: single nucleotide variant
Location: chr12:56344086 (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.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-leu718 (accessed [today's date]).

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