PRPH2 p.Arg123=
c.369G>A · VCV4891988
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.48 | GERP -3.6, phastCons 0.005 |
| Overall | ||
| CADD | 5.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,890 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000186%
3/1,613,926 alleles · very rare
exomes 2/1,461,892 · genomes 1/152,034 · 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.Arg123=
- Coding
- c.369G>A
- MANE Select
- NM_000322
- Type
- single nucleotide variant
- Location
- chr6:42721966 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
- Residue 123
- a UniProt-annotated variant site (in cacd2)
Similar variants
- PRPH2 p.Arg123Trp Conflicting classifications of pathogenicity ★ same residue
- 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
- PRPH2 c.582-2A>T Pathogenic ★★ same type
- PRPH2 c.828+1G>A Pathogenic ★★ same type
- PRPH2 c.828+1G>T Pathogenic ★★ same type
- PRPH2 c.828+2T>C Pathogenic/Likely 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-arg123 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown