Is STAT5B p.Arg241Gln (c.722G>A) pathogenic?

STAT5B p.Arg241Gln (c.722G>A) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1529); Very rare (popmax 0.00607%, amr); Associated with Inborn genetic diseases.

What condition is associated with STAT5B p.Arg241Gln (c.722G>A)?

STAT5B p.Arg241Gln (c.722G>A) is associated with Inborn genetic diseases (ClinVar).

How common is STAT5B p.Arg241Gln (c.722G>A) in the general population?

STAT5B p.Arg241Gln (c.722G>A) is very rare (popmax 0.00607%, amr) (gnomAD).

What do computational predictors say about STAT5B p.Arg241Gln (c.722G>A)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

STAT5B p.Arg241Gln

c.722G>A · VCV4176417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00607%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 0.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 4,042 bp · p 2.1e-06 · regional, not allelic
Overall
CADD	25.8	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 0.00607% Admixed American · 3/49,446 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000846%

Overall 0.000878% 13/1,480,768 alleles · very rare exomes 11/1,334,974 · genomes 2/145,794 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00607%	16,482
African / African-American	0.00143%	69,714
South Asian	0.00123%	81,156
European (non-Finnish)	0.00073%	137,013

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.Arg241Gln
Coding: c.722G>A
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42219423 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 241: an α-helix; the 'required for interaction with nmi' region

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.Arg241Trp 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-arg241gln (accessed [today's date]).

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