Is STAT5B p.Lys583fs (c.1749del) pathogenic?

STAT5B p.Lys583fs (c.1749del) is classified Pathogenic in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). No gnomAD frequency available for this variant; Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Lys583fs (c.1749del)?

STAT5B p.Lys583fs (c.1749del) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Lys583fs (c.1749del) in the general population?

STAT5B p.Lys583fs (c.1749del) is no gnomAD frequency available for this variant (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.Lys583fs

c.1749del · rs1202978138 · VCV2119313

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 14 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1

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

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: STAT5B
Protein: p.Lys583fs
Coding: c.1749del
MANE Select: NM_012448
dbSNP: rs1202978138
Type: Deletion
Location: chr17:42210429 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 583: an α-helix

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.Leu82fs 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-lys583fs (accessed [today's date]).

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