Is OCRL p.Ile55Val (c.163A>G) pathogenic?

OCRL p.Ile55Val (c.163A>G) is classified Uncertain significance in OCRL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-03). AlphaMissense: likely benign (0.0622); Very rare (popmax 0.000475%, nfe); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Ile55Val (c.163A>G)?

OCRL p.Ile55Val (c.163A>G) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ile55Val (c.163A>G) in the general population?

OCRL p.Ile55Val (c.163A>G) is very rare (popmax 0.000475%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Ile55Val (c.163A>G)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

OCRL p.Ile55Val

c.163A>G · rs989911294 · VCV2057620

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000475%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.87	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 4	GERP -1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	16.52	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 0.000475% European (non-Finnish) · 4/841,560 alleles

Filtering AF 0.000111% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.5e-05%

Overall 0.000347% 4/1,151,219 alleles · very rare exomes 3/1,038,662 · genomes 1/112,557 · 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.Ile55Val
Coding: c.163A>G
MANE Select: NM_000276
dbSNP: rs989911294
Type: single nucleotide variant
Location: chrX:129545001 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 55: 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 p.Ile55Leu Uncertain significance ★★ ⚠ same residue
OCRL p.Ile55Thr Uncertain significance ★★ ⚠ same residue
OCRL p.Ile55= Likely benign ★ same residue
OCRL p.Ile55Asn 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

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-ile55val (accessed [today's date]).

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