Is STAT5B p.Pro564Ser (c.1690C>T) pathogenic?

STAT5B p.Pro564Ser (c.1690C>T) is classified Uncertain significance in STAT5B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). AlphaMissense: likely benign (0.168); Ultra-rare (popmax 0.0253%, afr); Associated with Inborn genetic diseases.

What condition is associated with STAT5B p.Pro564Ser (c.1690C>T)?

STAT5B p.Pro564Ser (c.1690C>T) is associated with Inborn genetic diseases, growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Pro564Ser (c.1690C>T) in the general population?

STAT5B p.Pro564Ser (c.1690C>T) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about STAT5B p.Pro564Ser (c.1690C>T)?

AlphaMissense predicts likely benign (score 0.168) — an in-silico prediction, not a clinical call.

STAT5B p.Pro564Ser

c.1690C>T · rs561888537 · VCV2973961

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.168	likely benign
REVEL	0.68	pathogenic-leaning
SaProt	LLR -7.58	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,078 bp · p 1.5e-09 · regional, not allelic
Overall
CADD	28.8	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

Grpmax group 0.0253% African / African-American · 19/75,028 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00124% 20/1,614,058 alleles · ultra-rare exomes 9/1,461,810 · genomes 11/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,949
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Pro564Ser
Coding: c.1690C>T
MANE Select: NM_012448
dbSNP: rs561888537
Type: single nucleotide variant
Location: chr17:42210488 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 564: a β-strand

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

Disease context

Inborn genetic diseases — 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 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
STAT5B p.Arg121Leu 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-pro564ser (accessed [today's date]).

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