Is OCRL p.Val508Ile (c.1522G>A) pathogenic?

OCRL p.Val508Ile (c.1522G>A) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-30). AlphaMissense: likely benign (0.0725); Very rare (popmax 0.00246%, nfe); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Val508Ile (c.1522G>A)?

OCRL p.Val508Ile (c.1522G>A) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Val508Ile (c.1522G>A) in the general population?

OCRL p.Val508Ile (c.1522G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Val508Ile (c.1522G>A)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

OCRL p.Val508Ile

c.1522G>A · rs1358069294 · VCV1896669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -6.00	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 1.2	GERP -0.26, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	16.2	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 0.00246% European (non-Finnish) · 22/894,619 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00198% 24/1,209,645 alleles · very rare exomes 23/1,097,340 · genomes 1/112,305 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,664
Admixed American	0.00218%	45,811
Remaining individualsnot grpmax-eligible	0.0021%	47,587

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.Val508Ile
Coding: c.1522G>A
MANE Select: NM_000276
dbSNP: rs1358069294
Type: single nucleotide variant
Location: chrX:129569319 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 508: a β-strand; the 5-ppase domain; a UniProt-annotated variant site (in ocrl)

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-val508ile (accessed [today's date]).

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