PRPH2 p.Ser311=
c.933C>T · rs137853904 · VCV100554
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, afr)
Conditions
1
PRPH2-related disorder
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 -3.9 | GERP -3 |
| Overall | ||
| CADD | 3.331 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/75,034 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00812%
Overall
0.00297%
48/1,613,804 alleles · ultra-rare
exomes 35/1,461,534 · genomes 13/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0173% | 5,772 |
| South Asian | 0.00769% | 13,011 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
| Admixed American | 0.00333% | 30,006 |
| European (non-Finnish) | 0.00186% | 53,624 |
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.Ser311=
- Coding
- c.933C>T
- MANE Select
- NM_000322
- dbSNP
- rs137853904
- Type
- single nucleotide variant
- Location
- chr6:42698403 (GRCh38)
- Gene constraint
- LOEUF 0.773 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.56 · 1 PDB
Similar variants
- PRPH2 p.Ser311Arg Uncertain significance ★★ same residue
- PRPH2 p.Ser311Thr Uncertain significance ★ 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-ser311 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown