Is STAT5B p.Lys501fs (c.1500_1501dup) pathogenic?

STAT5B p.Lys501fs (c.15001501dup) is classified Pathogenic in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-07). Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Lys501fs (c.1500_1501dup)?

STAT5B p.Lys501fs (c.1500_1501dup) 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.Lys501fs

c.1500_1501dup · VCV4853469

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 13 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: STAT5B
Protein: p.Lys501fs
Coding: c.1500_1501dup
MANE Select: NM_012448
Type: Duplication
Location: chr17:42212162 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 501: a β-strand

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.Lys501Arg Uncertain significance ★★ ⚠ same residue
STAT5B p.Gln368fs Pathogenic ★★ same condition
STAT5B c.1776-21_1786dup Likely pathogenic ★ same condition
STAT5B p.Arg31fs Pathogenic ★ same condition
STAT5B p.Asn398fs Pathogenic same condition
STAT5B c.1906+1G>A Likely pathogenic ★★ same condition
STAT5B p.Leu142fs Pathogenic ★★ same condition
STAT5B p.Ala20Glu 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-lys501fs (accessed [today's date]).

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