PRPH2 p.Ala2Val
c.5C>T · rs761320905 · VCV2693843
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
1
PRPH2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.168 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP -0.34, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 17.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00186%
30/1,613,392 alleles · ultra-rare
exomes 27/1,461,226 · genomes 3/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| African / African-American | 0.00534% | 18,730 |
| South Asian | 0.00329% | 30,359 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| Admixed American | 0.00167% | 59,992 |
| European (non-Finnish) | 0.00161% | 62,107 |
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.Ala2Val
- Coding
- c.5C>T
- MANE Select
- NM_000322
- dbSNP
- rs761320905
- Type
- single nucleotide variant
- Location
- chr6:42722330 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
Similar variants
- PRPH2 p.Ala2Glu Uncertain significance ★★ same residue
- PRPH2 p.Ala2Thr Uncertain significance ★★ same residue
- PRPH2 p.Ala2= Likely benign ★★ same residue
- PRPH2 p.Ala2Ser 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
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-ala2val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown