Is STAT5B p.Ser787Pro (c.2359T>C) pathogenic?

STAT5B p.Ser787Pro (c.2359T>C) is classified Uncertain significance in STAT5B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1449); Ultra-rare (popmax 0.0253%, sas); Associated with growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant.

How common is STAT5B p.Ser787Pro (c.2359T>C) in the general population?

STAT5B p.Ser787Pro (c.2359T>C) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about STAT5B p.Ser787Pro (c.2359T>C)?

AlphaMissense predicts likely benign (score 0.1449) — an in-silico prediction, not a clinical call.

STAT5B p.Ser787Pro

Q: What condition is associated with STAT5B p.Ser787Pro (c.2359T>C)?

STAT5B p.Ser787Pro (c.2359T>C) is associated with growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant, growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

c.2359T>C · rs547016204 · VCV1037184

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1449 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.1449	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 696 bp · p 0.0011 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/90,806 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00156% 25/1,601,090 alleles · ultra-rare exomes 20/1,448,826 · genomes 5/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,948
Admixed American	0.00333%	29,998

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.Ser787Pro
Coding: c.2359T>C
MANE Select: NM_012448
dbSNP: rs547016204
Type: single nucleotide variant
Location: chr17:42201743 (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 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.Ser787= Likely benign ★ 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-ser787pro (accessed [today's date]).

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