PRPH p.Arg269=
c.807C>T · rs779483681 · VCV2642969
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -3.7 |
| Overall | ||
| CADD | 7.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,076 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00322%
52/1,613,680 alleles · ultra-rare
exomes 50/1,461,622 · genomes 2/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,076 |
| European (non-Finnish) | 0.00407% | 24,583 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,236 |
| Admixed American | 0.00167% | 59,982 |
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
- PRPH
- Protein
- p.Arg269=
- Coding
- c.807C>T
- MANE Select
- NM_006262
- dbSNP
- rs779483681
- Type
- single nucleotide variant
- Location
- chr12:49296993 (GRCh38)
- Gene constraint
- LOEUF 1.161 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.24
- Residue 269
- the if rod domain; the 'coil 2' region
Similar variants
- PRPH p.Glu233Lys Uncertain significance ★★ ⚠ same type
- PRPH p.Ile419Met Uncertain significance ★★ ⚠ same type
- PRPH c.1267+58T>C Benign ★★ same type
- PRPH c.1268-34T>C Benign ★★ same type
- PRPH c.703-163T>C Benign ★★ same type
- PRPH c.996+1G>A Benign/Likely benign ★★ same type
- PRPH c.-24G>C Benign ★★ same type
- PRPH p.Ala277Thr Likely benign ★★ 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/prph-p-arg269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown