TRPV4 p.Pro51=
c.153G>A · rs577306678 · VCV536853
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00934%, afr)
Conditions
2
Inborn genetic diseases
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 -16 | GERP -2.4 |
| Overall | ||
| CADD | 0.841 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00934%
African / African-American · 7/74,934 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00297%
48/1,613,604 alleles · very rare
exomes 43/1,461,450 · genomes 5/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00934% | 10,705 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
| European (non-Finnish) | 0.00297% | 33,713 |
| Admixed American | 0.00167% | 59,982 |
| South Asian | 0.0011% | 91,054 |
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
- TRPV4
- Protein
- p.Pro51=
- Coding
- c.153G>A
- MANE Select
- NM_021625
- dbSNP
- rs577306678
- Type
- single nucleotide variant
- Location
- chr12:109814644 (GRCh38)
- Gene constraint
- LOEUF 0.824 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.06 · 19 PDB
- Residue 51
- the 'disordered' region
Similar variants
- TRPV4 p.Pro51Leu Benign/Likely benign ★★ same residue
- TRPV4 p.Pro51Gln Uncertain significance ★ ⚠ same residue
- TRPV4 p.Arg186Gln Pathogenic/Likely pathogenic ★★ same condition
- TRPV4 p.Arg232Cys Pathogenic ★★ ⚠ same condition
- TRPV4 p.Arg269Cys Pathogenic ★★ ⚠ same condition
- TRPV4 p.Arg269His Pathogenic/Likely pathogenic ★★ same condition
- TRPV4 p.Arg315Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- TRPV4 p.Arg315Trp 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/trpv4-p-pro51 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown