STAT3 p.Lys409Ter
c.1225A>T · rs2144772188 · VCV2121657
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
STAT3 gain of function
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 24 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.21 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 0.78, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- STAT3
- Protein
- p.Lys409Ter
- Coding
- c.1225A>T
- MANE Select
- NM_139276
- dbSNP
- rs2144772188
- Type
- single nucleotide variant
- Location
- chr17:42329562 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.80 · 6 PDB
- Residue 409
- a β-strand
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-lys409ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown