Is OCRL p.Ala529= (c.1587C>G) pathogenic?

OCRL p.Ala529= (c.1587C>G) is classified Likely benign in OCRL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0385%, afr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Ala529= (c.1587C>G)?

OCRL p.Ala529= (c.1587C>G) is associated with oculocerebrorenal syndrome, Dent disease type 2 (ClinVar).

How common is OCRL p.Ala529= (c.1587C>G) in the general population?

OCRL p.Ala529= (c.1587C>G) is ultra-rare (popmax 0.0385%, afr) (gnomAD).

OCRL p.Ala529=

c.1587C>G · rs375634816 · VCV732134

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, afr)

Conditions

oculocerebrorenal syndrome

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 -0.79	GERP -5.4, phastCons 0.007
Overall
CADD	6.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0385% African / African-American · 22/57,177 alleles

Filtering AF 0.026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.0019% 23/1,209,178 alleles · ultra-rare exomes 9/1,097,198 · genomes 14/111,980 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0385%	2,599
Remaining individualsnot grpmax-eligible	0.0021%	47,591

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.Ala529=
Coding: c.1587C>G
MANE Select: NM_000276
dbSNP: rs375634816
Type: single nucleotide variant
Location: chrX:129569384 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 529: a β-strand; the 5-ppase domain

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oculocerebrorenal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Dent disease type 2

Similar variants

OCRL p.Ala529Asp Uncertain significance ★ ⚠ same residue
OCRL p.Ala529Thr Uncertain significance ★ ⚠ same residue
OCRL p.Ala529Ser Uncertain significance ★ ⚠ 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

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-ala529 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown