Is OCRL p.Arg95His (c.284G>A) pathogenic?

OCRL p.Arg95His (c.284G>A) is classified Benign/Likely benign in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-07). AlphaMissense: likely benign (0.0647); Ultra-rare (popmax 0.0207%, eas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg95His (c.284G>A)?

OCRL p.Arg95His (c.284G>A) is associated with oculocerebrorenal syndrome, Dent disease type 2 (ClinVar).

How common is OCRL p.Arg95His (c.284G>A) in the general population?

OCRL p.Arg95His (c.284G>A) is ultra-rare (popmax 0.0207%, eas) (gnomAD).

What do computational predictors say about OCRL p.Arg95His (c.284G>A)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

OCRL p.Arg95His

c.284G>A · rs770375201 · VCV1627578

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -7.19	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 -0.29	GERP -2
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	14.94	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 0.0207% East Asian · 7/33,777 alleles

Filtering AF 0.00967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0068%

Overall 0.00116% 14/1,209,592 alleles · ultra-rare exomes 14/1,098,029 · genomes 0/111,563 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0207%	4,825
Admixed American	0.011%	9,132
European (non-Finnish)	0.000223%	447,569

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.Arg95His
Coding: c.284G>A
MANE Select: NM_000276
dbSNP: rs770375201
Type: single nucleotide variant
Location: chrX:129557370 (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

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

Also linked: Dent disease type 2

Similar variants

OCRL p.Arg95Cys 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-arg95his (accessed [today's date]).

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