Is OCRL p.Leu657= (c.1971C>T) pathogenic?

OCRL p.Leu657= (c.1971C>T) is classified Likely benign in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-09). Very rare (popmax 0.00656%, amr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Leu657= (c.1971C>T)?

OCRL p.Leu657= (c.1971C>T) is associated with oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Leu657= (c.1971C>T) in the general population?

OCRL p.Leu657= (c.1971C>T) is very rare (popmax 0.00656%, amr) (gnomAD).

OCRL p.Leu657=

c.1971C>T · rs113252586 · VCV2801838

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00656%, amr)

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -5.4, phastCons 0.002
Overall
CADD	2.578	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00656% Admixed American · 3/45,750 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000882%

Overall 0.00149% 18/1,208,554 alleles · very rare exomes 17/1,096,762 · genomes 1/111,792 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00656%	15,250
Remaining individualsnot grpmax-eligible	0.00631%	15,851
East Asian	0.00296%	33,772
African / African-American	0.00175%	57,125
European (non-Finnish)	0.00112%	89,390

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.Leu657=
Coding: c.1971C>T
MANE Select: NM_000276
dbSNP: rs113252586
Type: single nucleotide variant
Location: chrX:129576408 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 657: a β-strand; the 'ash' region

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-leu657 (accessed [today's date]).

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