Is OCRL p.Asp451Asn (c.1351G>A) pathogenic?

OCRL p.Asp451Asn (c.1351G>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 2 submitters; last evaluated 2014-06-09). AlphaMissense: likely pathogenic (0.9815); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Asp451Asn (c.1351G>A)?

OCRL p.Asp451Asn (c.1351G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Asp451Asn (c.1351G>A) in the general population?

OCRL p.Asp451Asn (c.1351G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Asp451Asn (c.1351G>A)?

AlphaMissense predicts likely pathogenic (score 0.9815) — an in-silico prediction, not a clinical call.

OCRL p.Asp451Asn

c.1351G>A · rs137853838 · VCV68706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9815 · 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	0.9815	likely pathogenic
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -7.78	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 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	25.8	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.Asp451Asn
Coding: c.1351G>A
MANE Select: NM_000276
dbSNP: rs137853838
Type: single nucleotide variant
Location: chrX:129565878 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 451: 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.Asp451Gly Likely pathogenic ★ ⚠ same residue
OCRL p.Asp451= Likely benign ★ same residue
OCRL p.Asp451His Likely pathogenic ★ 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-asp451asn (accessed [today's date]).

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