Is OCRL p.Arg552His (c.1655G>A) pathogenic?

OCRL p.Arg552His (c.1655G>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.8951); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg552His (c.1655G>A)?

OCRL p.Arg552His (c.1655G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg552His (c.1655G>A) in the general population?

OCRL p.Arg552His (c.1655G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Arg552His (c.1655G>A)?

AlphaMissense predicts likely pathogenic (score 0.8951) — an in-silico prediction, not a clinical call.

OCRL p.Arg552His

c.1655G>A · rs2124417872 · VCV1428534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.8951	likely pathogenic
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	26.2	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.Arg552His
Coding: c.1655G>A
MANE Select: NM_000276
dbSNP: rs2124417872
Type: single nucleotide variant
Location: chrX:129575192 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB

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.Arg552= Conflicting classifications of pathogenicity ★ same residue
OCRL p.Arg552Cys 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
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-arg552his (accessed [today's date]).

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