Is STAT5B p.Ile285Val (c.853A>G) pathogenic?

STAT5B p.Ile285Val (c.853A>G) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-18). AlphaMissense: likely benign (0.0956); Absent from gnomAD v4.1; Associated with STAT5B-related growth hormone insensitivity syndrome.

What condition is associated with STAT5B p.Ile285Val (c.853A>G)?

STAT5B p.Ile285Val (c.853A>G) is associated with STAT5B-related growth hormone insensitivity syndrome (ClinVar).

How common is STAT5B p.Ile285Val (c.853A>G) in the general population?

STAT5B p.Ile285Val (c.853A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT5B p.Ile285Val (c.853A>G)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

STAT5B p.Ile285Val

c.853A>G · rs2080197805 · VCV873497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

STAT5B-related growth hormone insensitivity syndrome

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 0.89, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 629 bp · p 1.5e-08 · regional, not allelic
Overall
CADD	21.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STAT5B
Protein: p.Ile285Val
Coding: c.853A>G
MANE Select: NM_012448
dbSNP: rs2080197805
Type: single nucleotide variant
Location: chr17:42218859 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 285: 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

STAT5B-related growth hormone insensitivity syndrome

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.Asn477Ser Uncertain significance same condition
STAT5B p.Asn96His Uncertain significance ⚠ same condition
STAT5B p.Gly596= Likely benign 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-ile285val (accessed [today's date]).

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