GNAS p.Leu289fs
c.865del · VCV3643455
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GNAS
- Protein
- p.Leu289fs
- Coding
- c.865del
- MANE Select
- NM_000516
- Type
- Deletion
- Location
- chr20:58909975 (GRCh38)
- Gene constraint
- LOEUF 0.302 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 59.47 · 200 PDB
- Residue 289
- a β-strand; the g-alpha domain; the 'g4 motif' region; the 'disordered' region
Similar variants
- GNAS c.212+1_212+3del Likely pathogenic ★★ same type
- GNAS p.Asn371fs Pathogenic ★★ same type
- GNAS p.Asp173fs Pathogenic/Likely pathogenic ★★ same type
- GNAS p.His149fs Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Met1del Pathogenic/Likely pathogenic ★★ same type
- GNAS p.Tyr190fs Pathogenic ★★ same type
- GNAS p.Val117fs Pathogenic ★★ same type
- GNAS p.Gly297fs 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/gnas-p-leu289fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown