Is OCRL p.Arg552= (c.1656C>T) pathogenic?

OCRL p.Arg552= (c.1656C>T) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-22). Very rare (popmax 0.00738%, nfe); Associated with Dent disease type 2.

What condition is associated with OCRL p.Arg552= (c.1656C>T)?

OCRL p.Arg552= (c.1656C>T) is associated with Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg552= (c.1656C>T) in the general population?

OCRL p.Arg552= (c.1656C>T) is very rare (popmax 0.00738%, nfe) (gnomAD).

How is Dent disease inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

OCRL p.Arg552=

c.1656C>T · rs761645724 · VCV1028174

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00738%, nfe)

Conditions

Dent disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 1
Overall
CADD	16.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00738% European (non-Finnish) · 66/893,706 alleles

Filtering AF 0.00595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00543%

Overall 0.00554% 67/1,209,901 alleles · very rare exomes 67/1,096,155 · genomes 0/113,746 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00738%	13,541
Remaining individualsnot grpmax-eligible	0.0021%	47,584

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.Arg552=
Coding: c.1656C>T
MANE Select: NM_000276
dbSNP: rs761645724
Type: single nucleotide variant
Location: chrX:129575193 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dent disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocerebrorenal syndrome

For Dent disease (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

OCRL p.Arg552His Uncertain significance ★ ⚠ 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-arg552 (accessed [today's date]).

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