Is OCRL p.Arg500Ter (c.1498C>T) pathogenic?

OCRL p.Arg500Ter (c.1498C>T) is classified Pathogenic in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-20). Very rare (popmax 0.00173%, afr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg500Ter (c.1498C>T)?

OCRL p.Arg500Ter (c.1498C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg500Ter (c.1498C>T) in the general population?

OCRL p.Arg500Ter (c.1498C>T) is very rare (popmax 0.00173%, afr) (gnomAD).

OCRL p.Arg500Ter

c.1498C>T · rs398123287 · VCV666558

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.9, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,735 alleles

Overall 8.26e-05% 1/1,211,094 alleles · very rare exomes 1/1,097,549 · genomes 0/113,545 · joint denominator

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.Arg500Ter
Coding: c.1498C>T
MANE Select: NM_000276
dbSNP: rs398123287
Type: single nucleotide variant
Location: chrX:129569295 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 500: a β-strand; the 5-ppase domain; a UniProt-annotated variant site (in ocrl)

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

Similar variants

OCRL p.Arg500Gln Pathogenic ★★ same residue
OCRL p.Arg500Gly Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg500ter (accessed [today's date]).

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