Is OCRL p.Phe450= (c.1350C>T) pathogenic?

OCRL p.Phe450= (c.1350C>T) is classified Likely benign in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00596%, eas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Phe450= (c.1350C>T)?

OCRL p.Phe450= (c.1350C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Phe450= (c.1350C>T) in the general population?

OCRL p.Phe450= (c.1350C>T) is very rare (popmax 0.00596%, eas) (gnomAD).

OCRL p.Phe450=

c.1350C>T · rs1188979310 · VCV2890714

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00596%, eas)

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 -0.99	GERP -5.5, phastCons 0.004
Overall
CADD	4.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00596% East Asian · 2/33,557 alleles

Filtering AF 0.000987% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000369%

Overall 0.000857% 10/1,166,735 alleles · very rare exomes 9/1,055,457 · genomes 1/111,278 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00651%	15,372
East Asiangrpmax	0.00596%	16,778
European (non-Finnish)	0.000584%	171,332

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe450=
Coding: c.1350C>T
MANE Select: NM_000276
dbSNP: rs1188979310
Type: single nucleotide variant
Location: chrX:129565877 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 450: the 5-ppase domain

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-phe450 (accessed [today's date]).

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