Is OCRL p.Arg190His (c.569G>A) pathogenic?

OCRL p.Arg190His (c.569G>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1244); Very rare (popmax 0.00526%, sas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg190His (c.569G>A)?

OCRL p.Arg190His (c.569G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg190His (c.569G>A) in the general population?

OCRL p.Arg190His (c.569G>A) is very rare (popmax 0.00526%, sas) (gnomAD).

What do computational predictors say about OCRL p.Arg190His (c.569G>A)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

OCRL p.Arg190His

c.569G>A · rs776946722 · VCV1482748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00526%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	23.5	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 0.00526% South Asian · 3/57,003 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000687%

Overall 0.000495% 6/1,211,817 alleles · very rare exomes 6/1,098,117 · genomes 0/113,700 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00526%	19,001
Remaining individualsnot grpmax-eligible	0.0021%	47,650
European (non-Finnish)	0.000223%	447,726

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.Arg190His
Coding: c.569G>A
MANE Select: NM_000276
dbSNP: rs776946722
Type: single nucleotide variant
Location: chrX:129558848 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB

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.Arg190Pro Uncertain significance ★ ⚠ same residue
OCRL p.Arg190Cys Likely benign ★ same residue
OCRL p.Arg190Leu 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

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-arg190his (accessed [today's date]).

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