Is STAT1 p.Val734fs (c.2201_2208del) pathogenic?

STAT1 p.Val734fs (c.22012208del) is classified Uncertain significance in STAT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-29). No gnomAD frequency available for this variant; Associated with immunodeficiency 31B.

How common is STAT1 p.Val734fs (c.2201_2208del) in the general population?

STAT1 p.Val734fs (c.2201_2208del) is no gnomAD frequency available for this variant (gnomAD).

STAT1 p.Val734fs

Q: What condition is associated with STAT1 p.Val734fs (c.2201_2208del)?

STAT1 p.Val734fs (c.2201_2208del) 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.2201_2208del · rs1691780324 · VCV839216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (24 of 25, 30 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.94	GERP 0.66, phastCons 0.9

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STAT1
Protein: p.Val734fs
Coding: c.2201_2208del
MANE Select: NM_007315
dbSNP: rs1691780324
Type: Deletion
Location: chr2:190974860 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.78 · 10 PDB
Residue 734: an α-helix

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.Val734= Likely benign ★ same residue
STAT1 p.Ile30fs Pathogenic ★★ same condition
STAT1 p.Val339fs 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

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-val734fs (accessed [today's date]).

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