Is OCRL p.Ile274Val (c.820A>G) pathogenic?

OCRL p.Ile274Val (c.820A>G) is classified Likely benign in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). AlphaMissense: likely benign (0.0607); Very rare (popmax 0.00178%, afr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Ile274Val (c.820A>G)?

OCRL p.Ile274Val (c.820A>G) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ile274Val (c.820A>G) in the general population?

OCRL p.Ile274Val (c.820A>G) is very rare (popmax 0.00178%, afr) (gnomAD).

What do computational predictors say about OCRL p.Ile274Val (c.820A>G)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

OCRL p.Ile274Val

c.820A>G · rs1282050640 · VCV2814218

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -7.65	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 5.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	17.72	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 0.00178% African / African-American · 1/56,218 alleles

Overall 8.71e-05% 1/1,148,542 alleles · very rare exomes 0/1,036,165 · genomes 1/112,377 · 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.Ile274Val
Coding: c.820A>G
MANE Select: NM_000276
dbSNP: rs1282050640
Type: single nucleotide variant
Location: chrX:129560647 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 274: a UniProt-annotated variant site (in ocrl); the 5-ppase 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.Ile274Thr Likely pathogenic ★ same residue
OCRL p.Ile274fs Pathogenic ★ 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

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-ile274val (accessed [today's date]).

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