Is STAT5B p.Ser128Ala (c.382T>G) pathogenic?

STAT5B p.Ser128Ala (c.382T>G) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.0656); Absent from gnomAD v4.1.

How common is STAT5B p.Ser128Ala (c.382T>G) in the general population?

STAT5B p.Ser128Ala (c.382T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STAT5B p.Ser128Ala (c.382T>G)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

STAT5B p.Ser128Ala

c.382T>G · VCV4080385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.30	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,340 bp · p 0.55 · regional, not allelic
Overall
CADD	19.49	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.Ser128Ala
Coding: c.382T>G
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42223550 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 128: a modified residue (phosphoserine)

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

Similar variants

STAT5B c.1906+1G>A Likely pathogenic ★★ same type
STAT5B p.Ala20Glu Uncertain significance ★★ ⚠ same type
STAT5B p.Ala20Val Uncertain significance ★★ ⚠ same type
STAT5B p.Ala213Gly Uncertain significance ★★ ⚠ same type
STAT5B p.Ala213Ser Uncertain significance ★★ ⚠ same type
STAT5B p.Ala723Thr Uncertain significance ★★ ⚠ same type
STAT5B p.Ala785Thr Uncertain significance ★★ ⚠ same type
STAT5B p.Arg121Leu Uncertain significance ★★ ⚠ same type

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-ser128ala (accessed [today's date]).

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