GDF5 p.Val495=
c.1485G>A · rs2515417966 · VCV2978359
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP -0.18, phastCons 1 |
| Overall | ||
| CADD | 16.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,179,966 alleles
Overall
6.2e-05%
1/1,614,102 alleles · very rare
exomes 1/1,461,808 · genomes 0/152,294 · 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
- GDF5
- Protein
- p.Val495=
- Coding
- c.1485G>A
- MANE Select
- NM_000557
- dbSNP
- rs2515417966
- Type
- single nucleotide variant
- Location
- chr20:35433930 (GRCh38)
- Gene constraint
- LOEUF 0.71 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.04 · 15 PDB
- Residue 495
- a β-strand
Similar variants
- GDF5 p.Val495Leu Uncertain significance ★ ⚠ same residue
- GDF5 p.Arg156Ter Pathogenic/Likely pathogenic ★★ same type
- GDF5 p.Arg301Ter Pathogenic/Likely pathogenic ★★ ⚠ same type
- GDF5 p.Arg380Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- GDF5 p.Cys400Tyr Likely pathogenic ★★ same type
- GDF5 p.Gln210Ter Pathogenic/Likely pathogenic ★★ same type
- GDF5 p.Glu491Lys Pathogenic ★★ ⚠ same type
- GDF5 p.Trp297Ter Pathogenic/Likely pathogenic ★★ 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/gdf5-p-val495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown