Is OCRL p.Glu900Asp (c.2700A>C) pathogenic?

OCRL p.Glu900Asp (c.2700A>C) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0642); Very rare (popmax 8.27e-05%); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Glu900Asp (c.2700A>C)?

OCRL p.Glu900Asp (c.2700A>C) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Glu900Asp (c.2700A>C) in the general population?

OCRL p.Glu900Asp (c.2700A>C) is very rare (popmax 8.27e-05%) (gnomAD).

What do computational predictors say about OCRL p.Glu900Asp (c.2700A>C)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

OCRL p.Glu900Asp

c.2700A>C · VCV4125164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.27e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	17.88	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 8.27e-05%

Overall 8.27e-05% 1/1,209,144 alleles · very rare exomes 0/1,097,981 · genomes 1/111,163 · 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.Glu900Asp
Coding: c.2700A>C
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129590264 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 900: the rho-gap 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.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
OCRL p.Ser648Leu Uncertain significance ★★ ⚠ same condition
OCRL p.Val630Ala Uncertain significance ★★ ⚠ same condition
OCRL c.1602+11G>A Benign/Likely benign ★★ 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-glu900asp (accessed [today's date]).

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