Is OCRL p.Asn366Ser (c.1097A>G) pathogenic?

OCRL p.Asn366Ser (c.1097A>G) is classified Uncertain significance in OCRL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-17). AlphaMissense: likely benign (0.1251); Very rare (popmax 0.00173%, afr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Asn366Ser (c.1097A>G)?

OCRL p.Asn366Ser (c.1097A>G) is associated with oculocerebrorenal syndrome, Dent disease type 2 (ClinVar).

How common is OCRL p.Asn366Ser (c.1097A>G) in the general population?

OCRL p.Asn366Ser (c.1097A>G) is very rare (popmax 0.00173%, afr) (gnomAD).

What do computational predictors say about OCRL p.Asn366Ser (c.1097A>G)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

OCRL p.Asn366Ser

c.1097A>G · VCV3598019

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.792	moderately pathogenic-leaning
SaProt	LLR -8.54	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	24.7	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 0.00173% African / African-American · 1/57,871 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.00033% 4/1,211,673 alleles · very rare exomes 4/1,097,872 · genomes 0/113,801 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00173%	57,871
European (non-Finnish)	0.000335%	298,426

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.Asn366Ser
Coding: c.1097A>G
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129562639 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 366: the 5-ppase domain

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

Also linked: Dent disease type 2

Similar variants

OCRL p.Asn366= Likely benign ★ 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-asn366ser (accessed [today's date]).

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