Is OCRL p.Arg241Lys (c.722G>A) pathogenic?

OCRL p.Arg241Lys (c.722G>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: likely benign (0.1184); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg241Lys (c.722G>A)?

OCRL p.Arg241Lys (c.722G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg241Lys (c.722G>A) in the general population?

OCRL p.Arg241Lys (c.722G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Arg241Lys (c.722G>A)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

OCRL p.Arg241Lys

c.722G>A · rs2521879319 · VCV2966947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -2.2, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	21.3	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

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.Arg241Lys
Coding: c.722G>A
MANE Select: NM_000276
dbSNP: rs2521879319
Type: single nucleotide variant
Location: chrX:129559001 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 241: the 5-ppase domain; a β-strand

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

Disease context

oculocerebrorenal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OCRL p.Arg241Thr Conflicting classifications of pathogenicity ★ ⚠ 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-arg241lys (accessed [today's date]).

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