Is OCRL p.Val527Asp (c.1580T>A) pathogenic?

OCRL p.Val527Asp (c.1580T>A) is classified Likely pathogenic in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with Dent disease.

What condition is associated with OCRL p.Val527Asp (c.1580T>A)?

OCRL p.Val527Asp (c.1580T>A) is associated with Dent disease (ClinVar).

How common is OCRL p.Val527Asp (c.1580T>A) in the general population?

OCRL p.Val527Asp (c.1580T>A) 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.

What do computational predictors say about OCRL p.Val527Asp (c.1580T>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

OCRL p.Val527Asp

c.1580T>A · rs2521906486 · VCV1723236

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Dent disease

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 1% in OCRL
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -15.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val527Asp
Coding: c.1580T>A
MANE Select: NM_000276
dbSNP: rs2521906486
Type: single nucleotide variant
Location: chrX:129569377 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 527: a β-strand; the 5-ppase domain

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

Disease context

Dent disease — 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.2582-1G>C Likely pathogenic ★ same condition
OCRL p.Lys232fs Pathogenic ★ same condition
OCRL c.1244+1G>A Pathogenic/Likely pathogenic ★★ same type
OCRL c.1714-1G>A Pathogenic ★★ same type
OCRL c.2256+1G>T Likely pathogenic ★★ same type
OCRL c.560+1G>C Pathogenic/Likely pathogenic ★★ same type
OCRL c.940-11G>A Pathogenic/Likely pathogenic ★★ same type
OCRL p.Ala861Thr Pathogenic/Likely pathogenic ★★ ⚠ same type

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-val527asp (accessed [today's date]).

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