Is STAT5B p.Leu151Val (c.451C>G) pathogenic?

STAT5B p.Leu151Val (c.451C>G) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely benign (0.269); Very rare (popmax 8.47e-05%, nfe).

How common is STAT5B p.Leu151Val (c.451C>G) in the general population?

STAT5B p.Leu151Val (c.451C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about STAT5B p.Leu151Val (c.451C>G)?

AlphaMissense predicts likely benign (score 0.269) — an in-silico prediction, not a clinical call.

STAT5B p.Leu151Val

c.451C>G · VCV4883417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.269	likely benign
REVEL	0.348	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,340 bp · p 0.55 · regional, not allelic
Overall
CADD	23.8	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 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.2e-05% 1/1,614,174 alleles · very rare exomes 1/1,461,894 · genomes 0/152,280 · joint denominator

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.Leu151Val
Coding: c.451C>G
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42223481 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 151: an α-helix

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-leu151val (accessed [today's date]).

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