PRPH2 p.Cys213Arg
c.637T>C · rs61755802 · VCV98691
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
Conditions
3
PRPH2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.958 | 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 | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,020 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,188 alleles · very rare
exomes 2/1,461,892 · genomes 0/152,296 · 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.Cys213Arg
- Coding
- c.637T>C
- MANE Select
- NM_000322
- dbSNP
- rs61755802
- Type
- single nucleotide variant
- Location
- chr6:42704556 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
- Residue 213
- a UniProt-annotated variant site (in vmd3); a UniProt-annotated variant site (in mdpt1)
Similar variants
- PRPH2 p.Cys213Phe Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Cys213Ser Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Cys213Tyr Pathogenic/Likely pathogenic ★★ same residue
- PRPH2 p.Cys213Gly Likely pathogenic ★ same residue
- PRPH2 p.Cys213Trp 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
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-cys213arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown