Is STAT3 p.Lys707Glu (c.2119A>G) pathogenic?

STAT3 p.Lys707Glu (c.2119A>G) is classified Conflicting classifications of pathogenicity in STAT3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-29). AlphaMissense: likely pathogenic (0.5764); Absent from gnomAD v4.1; Associated with Inherited Immunodeficiency Diseases.

What condition is associated with STAT3 p.Lys707Glu (c.2119A>G)?

STAT3 p.Lys707Glu (c.2119A>G) is associated with Inherited Immunodeficiency Diseases, hyper-IgE recurrent infection syndrome 1, autosomal dominant (ClinVar).

How common is STAT3 p.Lys707Glu (c.2119A>G) in the general population?

STAT3 p.Lys707Glu (c.2119A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT3 p.Lys707Glu (c.2119A>G)?

AlphaMissense predicts likely pathogenic (score 0.5764) — an in-silico prediction, not a clinical call.

STAT3 p.Lys707Glu

c.2119A>G · rs1598381169 · VCV827745

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5764 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inherited Immunodeficiency Diseases

Computational evidence

Protein change
AlphaMissense	0.5764	likely pathogenic
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -4.92	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 327 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT3
Protein: p.Lys707Glu
Coding: c.2119A>G
MANE Select: NM_139276
dbSNP: rs1598381169
Type: single nucleotide variant
Location: chr17:42317207 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 6 PDB
Residue 707: a modified residue (n6-acetyllysine)

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

Disease context

Inherited Immunodeficiency Diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hyper-IgE recurrent infection syndrome 1, autosomal dominant

Similar variants

STAT3 p.Arg152Trp Pathogenic ★★ ⚠ same condition
STAT3 p.Arg278Cys Likely pathogenic ★★ same condition
STAT3 p.Arg335Trp Pathogenic/Likely pathogenic ★★ same condition
STAT3 p.Arg382Gln Pathogenic ★★ same condition
STAT3 p.Arg382Trp Pathogenic ★★ same condition
STAT3 p.Arg423Gln Pathogenic ★★ ⚠ same condition
STAT3 p.Asn466Ser Pathogenic ★★ ⚠ same condition
STAT3 p.Asn466Thr 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/stat3-p-lys707glu (accessed [today's date]).

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