Is OCRL p.His51Arg (c.152A>G) pathogenic?

OCRL p.His51Arg (c.152A>G) is classified Benign/Likely benign in OCRL (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0601); Rare (popmax 0.19%, sas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.His51Arg (c.152A>G)?

OCRL p.His51Arg (c.152A>G) is associated with oculocerebrorenal syndrome, intellectual disability, Dent disease type 2 (ClinVar).

How common is OCRL p.His51Arg (c.152A>G) in the general population?

OCRL p.His51Arg (c.152A>G) is rare (popmax 0.19%, sas) (gnomAD).

What do computational predictors say about OCRL p.His51Arg (c.152A>G)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

OCRL p.His51Arg

c.152A>G · rs764804719 · VCV1285062

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.19%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -5.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.029	GERP -3.8, phastCons 0.033
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	13.52	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 0.19% South Asian · 106/55,795 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.00963% 112/1,163,571 alleles · rare exomes 104/1,051,054 · genomes 8/112,517 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.19%	526
Remaining individualsnot grpmax-eligible	0.00868%	11,515
European (non-Finnish)	0.000235%	426,405

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.His51Arg
Coding: c.152A>G
MANE Select: NM_000276
dbSNP: rs764804719
Type: single nucleotide variant
Location: chrX:129544990 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 51: the ph domain

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: intellectual disability Dent disease type 2

Similar variants

OCRL p.His51Gln Uncertain significance ★ ⚠ 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-his51arg (accessed [today's date]).

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