PRPH2 p.Val209Phe
c.625G>T · rs753657349 · VCV437966
Pathogenic/Likely pathogenic
No assertion criteria
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Macular dystrophy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.927 | moderately pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PRPH2
- Protein
- p.Val209Phe
- Coding
- c.625G>T
- MANE Select
- NM_000322
- dbSNP
- rs753657349
- Type
- single nucleotide variant
- Location
- chr6:42704568 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
- Residue 209
- a UniProt-annotated variant site (in vmd3; increased protein expression)
Similar variants
- PRPH2 p.Val209Asp Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Val209Ile Likely pathogenic ★★ same residue
- PRPH2 p.Val209fs Pathogenic same residue
- PRPH2 p.Arg93fs Pathogenic/Likely pathogenic same condition
- PRPH2 p.Leu270fs Pathogenic/Likely pathogenic same condition
- PRPH2 c.581+1G>A Pathogenic ★★ same type
- PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same type
- PRPH2 c.582-1G>C 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/prph2-p-val209phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown