Is OCRL p.Arg810Ter (c.2428C>T) pathogenic?

OCRL p.Arg810Ter (c.2428C>T) is classified Pathogenic in OCRL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-01-08). Absent from gnomAD v4.1; Associated with Dent disease type 2.

What condition is associated with OCRL p.Arg810Ter (c.2428C>T)?

OCRL p.Arg810Ter (c.2428C>T) is associated with Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg810Ter (c.2428C>T) in the general population?

OCRL p.Arg810Ter (c.2428C>T) is absent from gnomAD v4.1 (gnomAD).

How is Dent disease inherited?

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

OCRL p.Arg810Ter

c.2428C>T · rs1569463775 · VCV594148

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Dent disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 22 of 24
Splicing
SpliceAI	Δ0.33	acceptor loss · deltas
Pangolin	Δ0.41	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.9	phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg810Ter
Coding: c.2428C>T
MANE Select: NM_000276
dbSNP: rs1569463775
Type: single nucleotide variant
Location: chrX:129588972 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 810: an α-helix; the rho-gap domain

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.Arg810Gln 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
OCRL p.Arg318Cys 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-arg810ter (accessed [today's date]).

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