Is STAT5B p.Leu82fs (c.245del) pathogenic?

STAT5B p.Leu82fs (c.245del) is classified Pathogenic in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-29). Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Leu82fs (c.245del)?

STAT5B p.Leu82fs (c.245del) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

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.Leu82fs

c.245del · VCV3641526

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

growth hormone insensitivity with immune dysregulation 1, autosomal recessive

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 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.004	GERP -4.2, phastCons 0.9

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

Variant & gene context

Gene: STAT5B
Protein: p.Leu82fs
Coding: c.245del
MANE Select: NM_012448
Type: Deletion
Location: chr17:42227569 (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.Leu142fs Pathogenic ★★ same condition
STAT5B p.Lys583fs Pathogenic ★ same condition
STAT5B p.Tyr405fs Pathogenic ★ same condition
STAT5B c.285+6_285+11del Uncertain significance ★ same condition
STAT5B p.Trp37_Ile38delinsCys Uncertain significance ★ same condition
STAT5B c.1257+19del Likely benign ★ same condition
STAT5B c.129-19_129-16del Likely benign ★ same condition
STAT5B c.2078-22_2078-14del 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/stat5b-p-leu82fs (accessed [today's date]).

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