Is OCRL p.Asp89His (c.265G>C) pathogenic?

OCRL p.Asp89His (c.265G>C) is classified Likely benign in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1992); Ultra-rare (popmax 0.0296%, eas); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Asp89His (c.265G>C)?

OCRL p.Asp89His (c.265G>C) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Asp89His (c.265G>C) in the general population?

OCRL p.Asp89His (c.265G>C) is ultra-rare (popmax 0.0296%, eas) (gnomAD).

What do computational predictors say about OCRL p.Asp89His (c.265G>C)?

AlphaMissense predicts likely benign (score 0.1992) — an in-silico prediction, not a clinical call.

OCRL p.Asp89His

c.265G>C · rs753369725 · VCV2199578

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0296%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.1992	likely benign
REVEL	0.579	indeterminate
SaProt	LLR -6.18	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 8.5	GERP 0.87, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	22.8	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 0.0296% East Asian · 10/33,768 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00174% 21/1,209,590 alleles · ultra-rare exomes 17/1,097,928 · genomes 4/111,662 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0296%	3,377
South Asian	0.0106%	9,464
Remaining individualsnot grpmax-eligible	0.0105%	9,519

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.Asp89His
Coding: c.265G>C
MANE Select: NM_000276
dbSNP: rs753369725
Type: single nucleotide variant
Location: chrX:129557351 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 89: 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

Similar variants

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
OCRL p.Arg318His 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-asp89his (accessed [today's date]).

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