Is STAT5B p.Asp500Glu (c.1500C>G) pathogenic?

STAT5B p.Asp500Glu (c.1500C>G) is classified Uncertain significance in STAT5B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.105); Very rare (popmax 6.19e-05%).

How common is STAT5B p.Asp500Glu (c.1500C>G) in the general population?

STAT5B p.Asp500Glu (c.1500C>G) is very rare (popmax 6.19e-05%) (gnomAD).

What do computational predictors say about STAT5B p.Asp500Glu (c.1500C>G)?

AlphaMissense predicts likely benign (score 0.105) — an in-silico prediction, not a clinical call.

STAT5B p.Asp500Glu

c.1500C>G · VCV4935188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.105 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.19e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.105	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -8.36	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 4.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,078 bp · p 1.5e-09 · regional, not allelic
Overall
CADD	19.93	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 6.19e-05%

Overall 6.19e-05% 1/1,614,208 alleles · very rare exomes 1/1,461,882 · genomes 0/152,326 · 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.Asp500Glu
Coding: c.1500C>G
MANE Select: NM_012448
Type: single nucleotide variant
Location: chr17:42212164 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 2 PDB
Residue 500: a β-strand

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

Similar variants

STAT5B p.Asp500Asn Uncertain significance ★ same residue
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

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-asp500glu (accessed [today's date]).

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