Is OCRL p.Tyr805= (c.2415C>T) pathogenic?

OCRL p.Tyr805= (c.2415C>T) is classified Benign/Likely benign in OCRL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0163%, nfe); Associated with Dent disease type 2.

What condition is associated with OCRL p.Tyr805= (c.2415C>T)?

OCRL p.Tyr805= (c.2415C>T) is associated with Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Tyr805= (c.2415C>T) in the general population?

OCRL p.Tyr805= (c.2415C>T) is ultra-rare (popmax 0.0163%, nfe) (gnomAD).

How is Dent disease inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

OCRL p.Tyr805=

c.2415C>T · rs377180274 · VCV1168649

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, nfe)

Conditions

Dent disease type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.8
Overall
CADD	0.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0163% European (non-Finnish) · 146/894,824 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.0131% 159/1,209,827 alleles · ultra-rare exomes 145/1,097,579 · genomes 14/112,248 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0163%	6,129
Admixed American	0.0153%	6,551
Remaining individualsnot grpmax-eligible	0.0105%	9,516
African / African-American	0.00175%	57,289

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.Tyr805=
Coding: c.2415C>T
MANE Select: NM_000276
dbSNP: rs377180274
Type: single nucleotide variant
Location: chrX:129588959 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 805: an α-helix; the rho-gap domain

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Dent disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oculocerebrorenal syndrome

For Dent disease (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

OCRL p.Tyr805Phe 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-tyr805 (accessed [today's date]).

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