GDF5 p.Pro165fs
c.490_491dup · VCV3377359
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
brachydactyly type C
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 1 of 2 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -6.1 | GERP -2.8 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GDF5
- Protein
- p.Pro165fs
- Coding
- c.490_491dup
- MANE Select
- NM_000557
- Type
- Duplication
- Location
- chr20:35437437 (GRCh38)
- Gene constraint
- LOEUF 0.71 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.04 · 15 PDB
- Residue 165
- the 'disordered' region
Similar variants
- GDF5 p.Ala69fs Pathogenic ★★ same condition
- GDF5 p.Gly271Ter Pathogenic/Likely pathogenic ★★ same condition
- GDF5 p.Cys400dup Uncertain significance ★★ same condition
- GDF5 p.Pro165= Likely benign ★ same residue
- GDF5 p.Arg301Ter Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GDF5 p.Arg331fs Pathogenic ★★ same condition
- GDF5 p.Ile167fs Pathogenic ★★ same condition
- GDF5 p.Leu53fs 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/gdf5-p-pro165fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown