Is STAT5B p.Gly596= (c.1788G>A) pathogenic?

STAT5B p.Gly596= (c.1788G>A) is classified Likely benign in STAT5B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-21). Very rare (popmax 0.00267%, afr); Associated with STAT5B-related disorder.

What condition is associated with STAT5B p.Gly596= (c.1788G>A)?

STAT5B p.Gly596= (c.1788G>A) is associated with STAT5B-related disorder (ClinVar).

How common is STAT5B p.Gly596= (c.1788G>A) in the general population?

STAT5B p.Gly596= (c.1788G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

STAT5B p.Gly596=

c.1788G>A · rs919883933 · VCV3047294

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

STAT5B-related disorder

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 0.93	GERP -3.9, phastCons 0.99
Overall
CADD	7.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,894 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,614,006 alleles · very rare exomes 0/1,461,888 · genomes 2/152,118 · joint denominator

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.Gly596=
Coding: c.1788G>A
MANE Select: NM_012448
dbSNP: rs919883933
Type: single nucleotide variant
Location: chr17:42210289 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 596: the sh2 domain

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

Disease context

STAT5B-related disorder

Similar variants

STAT5B p.Arg226Cys Uncertain significance ★★ ⚠ same condition
STAT5B p.Val362Met Uncertain significance ★★ ⚠ same condition
STAT5B p.Gln703Ter Likely pathogenic ★ same condition
STAT5B c.1258-5T>C Uncertain significance ★ same condition
STAT5B p.Ile285Val Uncertain significance ★ ⚠ same condition
STAT5B p.Asn477Ser Uncertain significance same condition
STAT5B p.Asn96His Uncertain significance ⚠ same condition
STAT5B p.Val435= Likely benign 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-gly596 (accessed [today's date]).

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