Is OCRL p.Cys498Arg (c.1492T>C) pathogenic?

OCRL p.Cys498Arg (c.1492T>C) is classified Pathogenic in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-01). AlphaMissense: likely pathogenic (0.9981); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Cys498Arg (c.1492T>C)?

OCRL p.Cys498Arg (c.1492T>C) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Cys498Arg (c.1492T>C) in the general population?

OCRL p.Cys498Arg (c.1492T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Cys498Arg (c.1492T>C)?

AlphaMissense predicts likely pathogenic (score 0.9981) — an in-silico prediction, not a clinical call.

OCRL p.Cys498Arg

c.1492T>C · rs2521906144 · VCV2022661

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9981 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.9981	likely pathogenic ✓ concordant with ClinVar · top 2% in OCRL
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -12.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCRL
Protein: p.Cys498Arg
Coding: c.1492T>C
MANE Select: NM_000276
dbSNP: rs2521906144
Type: single nucleotide variant
Location: chrX:129569289 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 498: 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 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
OCRL p.Arg318His 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-cys498arg (accessed [today's date]).

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