STAT3 p.Leu459=
c.1377G>A · rs2144718565 · VCV1158024
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
STAT3 gain of function
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 13.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,012 alleles
Overall
6.2e-05%
1/1,613,958 alleles · very rare
exomes 1/1,461,734 · genomes 0/152,224 · 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
- STAT3
- Protein
- p.Leu459=
- Coding
- c.1377G>A
- MANE Select
- NM_139276
- dbSNP
- rs2144718565
- Type
- single nucleotide variant
- Location
- chr17:42325050 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.80 · 6 PDB
- Residue 459
- an α-helix
Similar variants
- STAT3 p.Arg152Trp Pathogenic ★★ ⚠ same condition
- STAT3 p.Arg278Cys Likely pathogenic ★★ same condition
- STAT3 p.Arg335Trp Pathogenic/Likely pathogenic ★★ same condition
- STAT3 p.Arg382Gln Pathogenic ★★ same condition
- STAT3 p.Arg382Trp Pathogenic ★★ same condition
- STAT3 p.Arg423Gln Pathogenic ★★ ⚠ same condition
- STAT3 p.Asn466Ser Pathogenic ★★ ⚠ same condition
- STAT3 p.Asn466Thr Pathogenic/Likely pathogenic ★★ ⚠ 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/stat3-p-leu459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown