Is STAT5B p.Gln368fs (c.1102dup) pathogenic?

STAT5B p.Gln368fs (c.1102dup) is classified Pathogenic in STAT5B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00446%, eas); Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Gln368fs (c.1102dup)?

STAT5B p.Gln368fs (c.1102dup) is associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Gln368fs (c.1102dup) in the general population?

STAT5B p.Gln368fs (c.1102dup) is very rare (popmax 0.00446%, eas) (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.Gln368fs

c.1102dup · rs761761205 · VCV579749

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 9 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,840 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000744% 12/1,612,696 alleles · very rare exomes 11/1,460,934 · genomes 1/151,762 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00472%	21,166
East Asiangrpmax	0.00446%	22,420
Admixed American	0.00167%	59,926
Remaining individualsnot grpmax-eligible	0.0016%	62,450
African / African-American	0.00134%	74,786
South Asian	0.0011%	91,038
European (non-Finnish)	0.000254%	393,196

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: STAT5B
Protein: p.Gln368fs
Coding: c.1102dup
MANE Select: NM_012448
dbSNP: rs761761205
Type: Duplication
Location: chr17:42218217 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 368: 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 c.1776-21_1786dup Likely pathogenic ★ same condition
STAT5B p.Arg31fs Pathogenic ★ same condition
STAT5B p.Lys501fs 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
STAT5B p.Ala20Val 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-gln368fs (accessed [today's date]).

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