Is STAT5B p.Gln139= (c.417G>A) pathogenic?

STAT5B p.Gln139= (c.417G>A) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). Absent from gnomAD v4.1; Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

How common is STAT5B p.Gln139= (c.417G>A) in the general population?

STAT5B p.Gln139= (c.417G>A) is absent from gnomAD v4.1 (gnomAD).

How is Laron syndrome with immunodeficiency inherited?

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

STAT5B p.Gln139=

Q: What condition is associated with STAT5B p.Gln139= (c.417G>A)?

STAT5B p.Gln139= (c.417G>A) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

c.417G>A · rs2508776866 · VCV2706752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.72	acceptor gain · deltas
Pangolin	Δ0.79	gain · loss 0.53 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.6	GERP 2.1, phastCons 1
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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: STAT5B
Protein: p.Gln139=
Coding: c.417G>A
MANE Select: NM_012448
dbSNP: rs2508776866
Type: single nucleotide variant
Location: chr17:42223515 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB

Full STAT5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

growth hormone insensitivity with immune dysregulation 1, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Laron syndrome with immunodeficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

STAT5B p.Gln139Ter Pathogenic ★ same residue
STAT5B c.1906+1G>A Likely pathogenic ★★ same condition
STAT5B p.Ala20Glu Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala20Val Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala213Gly Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala213Ser Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala723Thr Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala785Thr 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/stat5b-p-gln139 (accessed [today's date]).

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