OCRL p.Ser522=
c.1566C>T · rs137853853 · VCV2716493
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00437%, amr)
Conditions
1
oculocerebrorenal syndrome
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 1.5 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 7.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00437%
Admixed American · 2/45,803 alleles
Filtering AF
0.000811%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000625%
Overall
0.00149%
18/1,209,076 alleles · very rare
exomes 12/1,096,933 · genomes 6/112,143 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00437% | 22,901 |
| African / African-American | 0.0035% | 28,594 |
| South Asian | 0.00176% | 56,827 |
| European (non-Finnish) | 0.00145% | 68,786 |
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
- OCRL
- Protein
- p.Ser522=
- Coding
- c.1566C>T
- MANE Select
- NM_000276
- dbSNP
- rs137853853
- Type
- single nucleotide variant
- Location
- chrX:129569363 (GRCh38)
- Structure
- AlphaFold pLDDT 82.91 · 5 PDB
- Residue 522
- a β-strand; the 5-ppase domain; a UniProt-annotated variant site (in ocrl)
Similar variants
- OCRL p.Ser522Asn Likely pathogenic ★ same residue
- OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same condition
- OCRL c.1714-1G>A Pathogenic ★★ same condition
- OCRL c.2256+1G>T Likely pathogenic ★★ same condition
- OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same condition
- OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same condition
- OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- OCRL p.Arg318Cys 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/ocrl-p-ser522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown