Is OCRL p.Ala529Ser (c.1585G>T) pathogenic?

OCRL p.Ala529Ser (c.1585G>T) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-28). AlphaMissense: likely benign (0.1062); Very rare (popmax 8.26e-05%); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Ala529Ser (c.1585G>T)?

OCRL p.Ala529Ser (c.1585G>T) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Ala529Ser (c.1585G>T) in the general population?

OCRL p.Ala529Ser (c.1585G>T) is very rare (popmax 8.26e-05%) (gnomAD).

What do computational predictors say about OCRL p.Ala529Ser (c.1585G>T)?

AlphaMissense predicts likely benign (score 0.1062) — an in-silico prediction, not a clinical call.

OCRL p.Ala529Ser

c.1585G>T · rs1219583539 · VCV2607111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1062 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.26e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.1062	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -2.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 0.78, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	15.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.26e-05%

Overall 8.26e-05% 1/1,210,600 alleles · very rare exomes 1/1,097,071 · genomes 0/113,529 · joint denominator

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.Ala529Ser
Coding: c.1585G>T
MANE Select: NM_000276
dbSNP: rs1219583539
Type: single nucleotide variant
Location: chrX:129569382 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 529: a β-strand; the 5-ppase domain

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

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCRL p.Ala529= Likely benign ★★ same residue
OCRL p.Ala529Asp Uncertain significance ★ ⚠ same residue
OCRL p.Ala529Thr Uncertain significance ★ ⚠ same residue
OCRL p.Arg25Pro Uncertain significance ★★ ⚠ same condition
OCRL p.Arg457His Uncertain significance ★★ ⚠ same condition
OCRL p.Asn196Thr Uncertain significance ★★ ⚠ same condition
OCRL p.Lys312Glu Uncertain significance ★★ ⚠ same condition
OCRL p.Lys701Arg Uncertain significance ★★ ⚠ 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-ala529ser (accessed [today's date]).

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