PRPH2 p.Ala85Thr
c.253G>A · rs760311433 · VCV1175211
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00834%, amr)
Conditions
1
PRPH2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.083 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP -1.8, phastCons 0.45 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic |
| Overall | ||
| CADD | 10.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00834%
Admixed American · 5/59,978 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00105%
17/1,614,026 alleles · very rare
exomes 16/1,461,894 · genomes 1/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00834% | 11,996 |
| African / African-American | 0.00267% | 37,453 |
| South Asian | 0.0022% | 45,542 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.000593% | 168,577 |
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.Ala85Thr
- Coding
- c.253G>A
- MANE Select
- NM_000322
- dbSNP
- rs760311433
- Type
- single nucleotide variant
- Location
- chr6:42722082 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
Similar variants
- 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
- PRPH2 p.Arg195Leu Pathogenic ★★ same condition
- PRPH2 p.Arg220Gln 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-ala85thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown