Is STAT1 p.Val339fs (c.1011_1012del) pathogenic?

STAT1 p.Val339fs (c.10111012del) is classified Pathogenic in STAT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-05). Very rare (popmax 0.0022%, sas); Associated with immunodeficiency 31B.

How common is STAT1 p.Val339fs (c.1011_1012del) in the general population?

STAT1 p.Val339fs (c.1011_1012del) is very rare (popmax 0.0022%, sas) (gnomAD).

STAT1 p.Val339fs

Q: What condition is associated with STAT1 p.Val339fs (c.1011_1012del)?

STAT1 p.Val339fs (c.1011_1012del) is associated with immunodeficiency 31B, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (ClinVar).

Q: How is Susceptibility to viral and mycobacterial infections due to STAT1 deficiency inherited?

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

c.1011_1012del · rs768767763 · VCV961842

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

immunodeficiency 31B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,078 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,614,138 alleles · very rare exomes 5/1,461,852 · genomes 0/152,286 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,539
African / African-American	0.00133%	75,032
European (non-Finnish)	0.000169%	590,012

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: STAT1
Protein: p.Val339fs
Coding: c.1011_1012del
MANE Select: NM_007315
dbSNP: rs768767763
Type: Deletion
Location: chr2:190991253 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB

Full STAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 31B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency

For Susceptibility to viral and mycobacterial infections due to STAT1 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

STAT1 p.Val339Phe Likely pathogenic ★ same residue
STAT1 p.Ile30fs Pathogenic ★★ same condition
STAT1 p.Asp257fs Pathogenic ★ same condition
STAT1 p.Glu411fs Pathogenic ★ same condition
STAT1 p.Ile232fs Pathogenic ★ same condition
STAT1 p.Ile612fs Pathogenic ★ same condition
STAT1 p.Leu667fs Pathogenic ★ same condition
STAT1 p.Lys361fs 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/stat1-p-val339fs (accessed [today's date]).

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