Is OCRL p.Arg95Cys (c.283C>T) pathogenic?

OCRL p.Arg95Cys (c.283C>T) is classified Likely benign in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0458%, mid); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Arg95Cys (c.283C>T)?

OCRL p.Arg95Cys (c.283C>T) is associated with Nephrolithiasis/nephrocalcinosis, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg95Cys (c.283C>T) in the general population?

OCRL p.Arg95Cys (c.283C>T) is ultra-rare (popmax 0.0458%, mid) (gnomAD).

What do computational predictors say about OCRL p.Arg95Cys (c.283C>T)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

OCRL p.Arg95Cys

c.283C>T · rs759942057 · VCV2905546

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP 0.29
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.0458% Middle Eastern · 2/4,369 alleles

Filtering AF 0.0081% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00207% 25/1,209,555 alleles · ultra-rare exomes 20/1,098,051 · genomes 5/111,504 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0458%	2,184
East Asian	0.00592%	16,892
European (non-Finnish)	0.00223%	44,756
Admixed American	0.00219%	45,648

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.Arg95Cys
Coding: c.283C>T
MANE Select: NM_000276
dbSNP: rs759942057
Type: single nucleotide variant
Location: chrX:129557369 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 95: the ph domain; a β-strand

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

Also linked: oculocerebrorenal syndrome

Similar variants

OCRL p.Arg95His Benign/Likely benign ★★ 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-arg95cys (accessed [today's date]).

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