Is OCRL p.Arg580Trp (c.1738C>T) pathogenic?

OCRL p.Arg580Trp (c.1738C>T) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.6336); Very rare (popmax 0.00324%, nfe); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg580Trp (c.1738C>T)?

OCRL p.Arg580Trp (c.1738C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg580Trp (c.1738C>T) in the general population?

OCRL p.Arg580Trp (c.1738C>T) is very rare (popmax 0.00324%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Arg580Trp (c.1738C>T)?

AlphaMissense predicts likely pathogenic (score 0.6336) — an in-silico prediction, not a clinical call.

OCRL p.Arg580Trp

c.1738C>T · VCV4740568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00324%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.6336	likely pathogenic
REVEL	0.726	pathogenic-leaning
SaProt	LLR -11.99	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 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00324% European (non-Finnish) · 29/895,420 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.00239% 29/1,211,764 alleles · very rare exomes 29/1,098,051 · genomes 0/113,713 · 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.Arg580Trp
Coding: c.1738C>T
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129575921 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 580: the 'ash' region

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.Arg580Gln 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
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-arg580trp (accessed [today's date]).

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