Is STAT5B p.Arg290Gln (c.869G>A) pathogenic?

STAT5B p.Arg290Gln (c.869G>A) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). AlphaMissense: likely pathogenic (0.9637); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with STAT5B p.Arg290Gln (c.869G>A)?

STAT5B p.Arg290Gln (c.869G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT5B p.Arg290Gln (c.869G>A) in the general population?

STAT5B p.Arg290Gln (c.869G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about STAT5B p.Arg290Gln (c.869G>A)?

AlphaMissense predicts likely pathogenic (score 0.9637) — an in-silico prediction, not a clinical call.

STAT5B p.Arg290Gln

c.869G>A · VCV4176414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9637	likely pathogenic
REVEL	0.606	indeterminate
SaProt	LLR -11.92	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 7.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 629 bp · p 1.5e-08 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00446% East Asian · 2/44,886 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000868% 14/1,613,532 alleles · very rare exomes 11/1,461,426 · genomes 3/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
South Asian	0.0022%	45,531
Admixed American	0.00167%	59,988
European (non-Finnish)	0.000763%	131,090

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.Arg290Gln
Coding: c.869G>A
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42218843 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 290: the 'required for interaction with nmi' region; an α-helix

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

Similar variants

STAT5B p.Arg290Pro Uncertain significance ★ ⚠ same residue
STAT5B p.Ala213Ser Uncertain significance ★★ ⚠ same condition
STAT5B p.Ala723Thr Uncertain significance ★★ ⚠ same condition
STAT5B p.Arg200Gln Uncertain significance ★★ ⚠ same condition
STAT5B p.Arg353Cys Uncertain significance ★★ ⚠ same condition
STAT5B p.Arg768Cys Uncertain significance ★★ ⚠ same condition
STAT5B p.Asn741Tyr Uncertain significance ★★ ⚠ same condition
STAT5B p.Asp157Tyr 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-arg290gln (accessed [today's date]).

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