Is OCRL p.Val380Ala (c.1139T>C) pathogenic?

OCRL p.Val380Ala (c.1139T>C) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: ambiguous (0.4235); Absent from gnomAD v4.1; Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Val380Ala (c.1139T>C)?

OCRL p.Val380Ala (c.1139T>C) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Val380Ala (c.1139T>C) in the general population?

OCRL p.Val380Ala (c.1139T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Val380Ala (c.1139T>C)?

AlphaMissense predicts ambiguous (score 0.4235) — an in-silico prediction, not a clinical call.

OCRL p.Val380Ala

c.1139T>C · rs2521890114 · VCV2805761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4235 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.4235	ambiguous
REVEL	0.482	indeterminate
SaProt	LLR -6.92	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.51, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	24.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCRL
Protein: p.Val380Ala
Coding: c.1139T>C
MANE Select: NM_000276
dbSNP: rs2521890114
Type: single nucleotide variant
Location: chrX:129562681 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 380: the 5-ppase domain; a turn

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.Val380Met 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
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-val380ala (accessed [today's date]).

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