STAT3 p.Trp562Ter
c.1685G>A · VCV4935215
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
STAT3-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 19 of 24 |
| Splicing | ||
| SpliceAI | Δ0.42 | acceptor gain · deltas |
| Pangolin | Δ0.53 | gain · loss 0.34 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 51.0 | 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.Trp562Ter
- Coding
- c.1685G>A
- MANE Select
- NM_139276
- Type
- single nucleotide variant
- Location
- chr17:42323323 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 85.80 · 6 PDB
- Residue 562
- an α-helix
Disease context
STAT3-related disorder
Similar variants
- STAT3 p.Arg152Trp Pathogenic ★★ ⚠ same condition
- STAT3 p.Gly421Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- STAT3 p.His332Tyr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- STAT3 p.Thr716Met Pathogenic ★★ ⚠ same condition
- STAT3 p.Cys718Tyr Uncertain significance ★★ ⚠ same condition
- STAT3 c.551-1G>A Likely pathogenic ★ same condition
- STAT3 p.Asn466Asp Likely pathogenic ★ same condition
- STAT3 p.Lys340Glu 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-trp562ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown