PRPH2 p.Trp97Arg
c.289T>C · VCV3676867
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Conditions
1
PRPH2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.375 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 22.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/75,048 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000494%
Overall
0.000434%
7/1,614,178 alleles · very rare
exomes 7/1,461,882 · genomes 0/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 25,016 |
| Admixed American | 0.00167% | 60,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
| European (non-Finnish) | 0.000169% | 590,016 |
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.Trp97Arg
- Coding
- c.289T>C
- MANE Select
- NM_000322
- Type
- single nucleotide variant
- Location
- chr6:42722046 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
Similar variants
- PRPH2 p.Trp97Ter Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Trp97fs Pathogenic/Likely pathogenic ★★ 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
- PRPH2 c.828+3A>T Pathogenic ★★ same condition
- PRPH2 p.Arg142Trp 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-trp97arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown