GDF5 p.Pro152=
c.456C>T · rs748783641 · VCV3015539
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.95 | GERP -5 |
| Overall | ||
| CADD | 4.961 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,090 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.000805%
13/1,613,950 alleles · very rare
exomes 12/1,461,786 · genomes 1/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,386 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| African / African-American | 0.00134% | 74,906 |
| European (non-Finnish) | 0.000254% | 393,329 |
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.Pro152=
- Coding
- c.456C>T
- MANE Select
- NM_000557
- dbSNP
- rs748783641
- Type
- single nucleotide variant
- Location
- chr20:35437473 (GRCh38)
- Gene constraint
- LOEUF 0.71 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.04 · 15 PDB
- Residue 152
- the 'disordered' region
Similar variants
- 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
- GDF5 p.Ala254Asp 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/gdf5-p-pro152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown