Is OCRL p.Asp451= (c.1353C>T) pathogenic?

OCRL p.Asp451= (c.1353C>T) is classified Likely benign in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). Very rare (popmax 0.000353%, nfe); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Asp451= (c.1353C>T)?

OCRL p.Asp451= (c.1353C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Asp451= (c.1353C>T) in the general population?

OCRL p.Asp451= (c.1353C>T) is very rare (popmax 0.000353%, nfe) (gnomAD).

OCRL p.Asp451=

c.1353C>T · rs2521898951 · VCV2831889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000353%, nfe)

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000353% European (non-Finnish) · 3/849,177 alleles

Filtering AF 9.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.6e-05%

Overall 0.000259% 3/1,159,913 alleles · very rare exomes 3/1,046,956 · genomes 0/112,957 · 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.Asp451=
Coding: c.1353C>T
MANE Select: NM_000276
dbSNP: rs2521898951
Type: single nucleotide variant
Location: chrX:129565880 (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.Asp451Asn Uncertain significance ★ ⚠ 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-asp451 (accessed [today's date]).

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