Is OCRL p.His61Arg (c.182A>G) pathogenic?

OCRL p.His61Arg (c.182A>G) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-06-11). AlphaMissense: likely benign (0.0572); Very rare (popmax 0.00217%, amr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.His61Arg (c.182A>G)?

OCRL p.His61Arg (c.182A>G) is associated with oculocerebrorenal syndrome, Dent disease type 2 (ClinVar).

How common is OCRL p.His61Arg (c.182A>G) in the general population?

OCRL p.His61Arg (c.182A>G) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about OCRL p.His61Arg (c.182A>G)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

OCRL p.His61Arg

c.182A>G · rs1286748036 · VCV2884407

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -4.92	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 8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	17.52	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 0.00217% Admixed American · 1/45,981 alleles

Overall 9.06e-05% 1/1,103,987 alleles · very rare exomes 1/990,184 · genomes 0/113,803 · joint denominator

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.His61Arg
Coding: c.182A>G
MANE Select: NM_000276
dbSNP: rs1286748036
Type: single nucleotide variant
Location: chrX:129545020 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 61: 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.His61Tyr Uncertain significance ★ ⚠ same residue
OCRL p.His61= 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

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-his61arg (accessed [today's date]).

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