Is STAT3 p.Phe561del (c.1682_1684del) pathogenic?

STAT3 p.Phe561del (c.16821684del) is classified Uncertain significance in STAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-23). Absent from gnomAD; Associated with hyper-IgE recurrent infection syndrome 1, autosomal dominant.

What condition is associated with STAT3 p.Phe561del (c.1682_1684del)?

STAT3 p.Phe561del (c.1682_1684del) is associated with hyper-IgE recurrent infection syndrome 1, autosomal dominant (ClinVar).

How common is STAT3 p.Phe561del (c.1682_1684del) in the general population?

STAT3 p.Phe561del (c.1682_1684del) is absent from gnomAD (gnomAD).

STAT3 p.Phe561del

Q: How is Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency inherited?

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

c.1682_1684del · rs2509224421 · VCV2927224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hyper-IgE recurrent infection syndrome 1, autosomal dominant

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 7.7	GERP 1.9, phastCons 1

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: STAT3
Protein: p.Phe561del
Coding: c.1682_1684del
MANE Select: NM_139276
dbSNP: rs2509224421
Type: Deletion
Location: chr17:42323324 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 6 PDB
Residue 561: an α-helix; a UniProt-annotated variant site (in)

Full STAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hyper-IgE recurrent infection syndrome 1, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

STAT3 c.551-137_551-18del Benign ★★ same condition
STAT3 c.1110-2_1115del Uncertain significance ★ same condition
STAT3 p.Asn553fs Uncertain significance ★ same condition
STAT3 p.Asp502fs Uncertain significance ★ same condition
STAT3 p.Gly656_Met660del Uncertain significance ★ same condition
STAT3 p.Thr600del Uncertain significance ★ same condition
STAT3 p.Val299del Uncertain significance ★ same condition
STAT3 c.1049+18del Likely benign ★ 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/stat3-p-phe561del (accessed [today's date]).

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