Is OCRL p.Trp486Ter (c.1458G>A) pathogenic?

OCRL p.Trp486Ter (c.1458G>A) is classified Pathogenic in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). No allele count reported in gnomAD v4.1 (AN 1,150,249); Associated with Dent disease type 2.

What condition is associated with OCRL p.Trp486Ter (c.1458G>A)?

OCRL p.Trp486Ter (c.1458G>A) is associated with Dent disease type 2 (ClinVar).

How common is OCRL p.Trp486Ter (c.1458G>A) in the general population?

OCRL p.Trp486Ter (c.1458G>A) is no allele count reported in gnomAD v4.1 (AN 1,150,249) (gnomAD).

How is Dent disease inherited?

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

OCRL p.Trp486Ter

c.1458G>A · rs2124410812 · VCV1685997

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,150,249)

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 14 of 24
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Overall
CADD	43.0	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

No allele count reported in gnomAD v4.1 (AN 1,150,249). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OCRL
Protein: p.Trp486Ter
Coding: c.1458G>A
MANE Select: NM_000276
dbSNP: rs2124410812
Type: single nucleotide variant
Location: chrX:129567355 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 486: the 5-ppase domain; a β-strand

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

For Dent disease (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

OCRL c.1244+1G>A Pathogenic/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.Arg318Cys Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Arg493Trp Pathogenic ★★ same condition
OCRL p.Arg695Ter Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Arg810Ter 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-trp486ter (accessed [today's date]).

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