Is OCRL p.Asn79Asp (c.235A>G) pathogenic?

OCRL p.Asn79Asp (c.235A>G) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-03-03). AlphaMissense: likely benign (0.0889); Ultra-rare (popmax 0.0316%, afr); Associated with oculocerebrorenal syndrome.

What condition is associated with OCRL p.Asn79Asp (c.235A>G)?

OCRL p.Asn79Asp (c.235A>G) is associated with oculocerebrorenal syndrome, Dent disease type 2 (ClinVar).

How common is OCRL p.Asn79Asp (c.235A>G) in the general population?

OCRL p.Asn79Asp (c.235A>G) is ultra-rare (popmax 0.0316%, afr) (gnomAD).

What do computational predictors say about OCRL p.Asn79Asp (c.235A>G)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

OCRL p.Asn79Asp

c.235A>G · rs146556695 · VCV2040267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0316%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculocerebrorenal syndrome

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -6.49	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 8	GERP 0.64, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 19 kb · p 0.85 · regional, not allelic
Overall
CADD	19.33	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 0.0316% African / African-American · 18/56,873 alleles

Filtering AF 0.0204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.0021% 25/1,193,037 alleles · ultra-rare exomes 11/1,081,139 · genomes 14/111,898 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0316%	3,160
Middle Eastern	0.0231%	4,331
Remaining individualsnot grpmax-eligible	0.00213%	47,010
European (non-Finnish)	0.000568%	176,005

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.Asn79Asp
Coding: c.235A>G
MANE Select: NM_000276
dbSNP: rs146556695
Type: single nucleotide variant
Location: chrX:129548598 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 79: the ph 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 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-asn79asp (accessed [today's date]).

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