Is OCRL p.Arg886His (c.2657G>A) pathogenic?

OCRL p.Arg886His (c.2657G>A) is classified Uncertain significance in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.1285); Very rare (popmax 0.00704%, sas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Arg886His (c.2657G>A)?

OCRL p.Arg886His (c.2657G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Arg886His (c.2657G>A) in the general population?

OCRL p.Arg886His (c.2657G>A) is very rare (popmax 0.00704%, sas) (gnomAD).

What do computational predictors say about OCRL p.Arg886His (c.2657G>A)?

AlphaMissense predicts likely benign (score 0.1285) — an in-silico prediction, not a clinical call.

OCRL p.Arg886His

c.2657G>A · rs897622079 · VCV2155057

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00704%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.1285	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.87	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 6.5	phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	23.0	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 0.00704% South Asian · 4/56,800 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00311%

Overall 0.00405% 49/1,209,488 alleles · very rare exomes 46/1,098,030 · genomes 3/111,458 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00704%	14,200
European (non-Finnish)	0.00469%	21,311
African / African-American	0.00351%	28,518
East Asian	0.00296%	33,753

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.Arg886His
Coding: c.2657G>A
MANE Select: NM_000276
dbSNP: rs897622079
Type: single nucleotide variant
Location: chrX:129590221 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 886: an α-helix; the rho-gap 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

Similar variants

OCRL p.Arg886= 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-arg886his (accessed [today's date]).

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