Is STAT5B p.Gln786= (c.2358A>G) pathogenic?

STAT5B p.Gln786= (c.2358A>G) is classified Likely benign in STAT5B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). Very rare (popmax 0.00661%, sas); Associated with Inborn genetic diseases.

What condition is associated with STAT5B p.Gln786= (c.2358A>G)?

STAT5B p.Gln786= (c.2358A>G) is associated with Inborn genetic diseases, growth hormone insensitivity with immune dysregulation 1, autosomal recessive (ClinVar).

How common is STAT5B p.Gln786= (c.2358A>G) in the general population?

STAT5B p.Gln786= (c.2358A>G) is very rare (popmax 0.00661%, sas) (gnomAD).

STAT5B p.Gln786=

c.2358A>G · rs568497349 · VCV1059610

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00661%, sas)

Conditions

Inborn genetic diseases

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 -0.22	GERP 0.89, phastCons 0.22
Overall
CADD	7.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% South Asian · 6/90,826 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.00119% 19/1,600,786 alleles · very rare exomes 15/1,448,548 · genomes 4/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00661%	15,138
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.00484%	20,679
African / African-American	0.00401%	24,927
European (non-Finnish)	0.000343%	291,962

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.Gln786=
Coding: c.2358A>G
MANE Select: NM_012448
dbSNP: rs568497349
Type: single nucleotide variant
Location: chr17:42201744 (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

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-gln786 (accessed [today's date]).

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