PRPH2 p.Trp174Arg
c.520T>A · rs1395223954 · VCV1175218
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
PRPH2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.933 | strongly pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 29.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,034 alleles
Overall
6.19e-05%
1/1,614,220 alleles · very rare
exomes 1/1,461,890 · genomes 0/152,330 · 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
- PRPH2
- Protein
- p.Trp174Arg
- Coding
- c.520T>A
- MANE Select
- NM_000322
- dbSNP
- rs1395223954
- Type
- single nucleotide variant
- Location
- chr6:42721815 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
Similar variants
- PRPH2 p.Trp174Cys Likely pathogenic ★★ same residue
- PRPH2 p.Trp174Ter Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Trp174Gly Likely pathogenic ★ same residue
- PRPH2 p.Trp174Ser Uncertain significance ★ same residue
- PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
- PRPH2 c.828+1G>A Pathogenic ★★ same condition
- PRPH2 c.828+1G>T Pathogenic ★★ same condition
- PRPH2 c.828+2T>C 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/prph2-p-trp174arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown