Is STAT5B p.Pro367= (c.1101C>A) pathogenic?

STAT5B p.Pro367= (c.1101C>A) is classified Benign/Likely benign in STAT5B (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-09). Common (popmax 5.71%, mid) — too common for a highly-penetrant pathogenic allele; Associated with growth hormone insensitivity with immune dysregulation 1, autosomal recessive.

What condition is associated with STAT5B p.Pro367= (c.1101C>A)?

STAT5B p.Pro367= (c.1101C>A) 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.Pro367=

Q: How common is STAT5B p.Pro367= (c.1101C>A) in the general population?

STAT5B p.Pro367= (c.1101C>A) is common (popmax 5.71%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1101C>A · rs61749920 · VCV199127

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 5.71%, mid) — too common for a highly-penetrant pathogenic allele

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -4.2
Overall
CADD	9.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.71% Middle Eastern · 346/6,062 alleles

Filtering AF 5.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.33%

Overall 2.46% 39,726/1,614,132 alleles · common exomes 36,861/1,461,888 · genomes 2,865/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	5.71%	18
South Asian	5.51%	18
Ashkenazi Jewishnot grpmax-eligible	5.02%	20
Remaining individualsnot grpmax-eligible	2.93%	34
European (non-Finnish)	2.42%	41
Finnishnot grpmax-eligible	1.87%	53
Admixed American	1.57%	64
African / African-American	0.428%	234
Amishnot grpmax-eligible	0.219%	456
East Asian	0.0156%	6,412

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.Pro367=
Coding: c.1101C>A
MANE Select: NM_012448
dbSNP: rs61749920
Type: single nucleotide variant
Location: chr17:42218219 (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.Pro367Arg Uncertain significance ★ ⚠ same residue
STAT5B p.Pro367His Uncertain significance ★ ⚠ same residue
STAT5B p.Pro367Leu Uncertain significance ★ ⚠ 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

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-pro367 (accessed [today's date]).

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