Is STAT5B p.Gln177Pro (c.530A>C) pathogenic?

STAT5B p.Gln177Pro (c.530A>C) is classified Pathogenic in STAT5B (ClinVar, No assertion criteria, 2 submitters; last evaluated 2020-08-21). AlphaMissense: likely pathogenic (0.9944); Absent from gnomAD v4.1; Associated with growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant.

What condition is associated with STAT5B p.Gln177Pro (c.530A>C)?

STAT5B p.Gln177Pro (c.530A>C) is associated with growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant, growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Gln177Pro (c.530A>C) in the general population?

STAT5B p.Gln177Pro (c.530A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT5B p.Gln177Pro (c.530A>C)?

AlphaMissense predicts likely pathogenic (score 0.9944) — an in-silico prediction, not a clinical call.

STAT5B p.Gln177Pro

c.530A>C · rs1555549674 · VCV522611

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9944 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.9944	likely pathogenic ✓ concordant with ClinVar
REVEL	0.634	indeterminate
SaProt	LLR -14.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 4,042 bp · p 2.1e-06 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT5B
Protein: p.Gln177Pro
Coding: c.530A>C
MANE Select: NM_012448
dbSNP: rs1555549674
Type: single nucleotide variant
Location: chr17:42223402 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 177: an α-helix; a UniProt-annotated variant site (in ghisid2; exhibits strong growth hormone-induced phosphorylation, but no subsequent nuclear localization; when forming homodimers with the wild-type protein, may also prevent its nuclear localization following growth hormone-stimulation)

Full STAT5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Similar variants

STAT5B p.Gln177Arg 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
STAT5B p.Ala723Thr Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala785Thr 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-gln177pro (accessed [today's date]).

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