Is OCRL p.Ser489= (c.1467T>C) pathogenic?

OCRL p.Ser489= (c.1467T>C) is classified Conflicting classifications of pathogenicity in OCRL (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-14). Very rare (popmax 0.00112%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Ser489= (c.1467T>C)?

OCRL p.Ser489= (c.1467T>C) is associated with Nephrolithiasis/nephrocalcinosis, Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Ser489= (c.1467T>C) in the general population?

OCRL p.Ser489= (c.1467T>C) is very rare (popmax 0.00112%, nfe) (gnomAD).

OCRL p.Ser489=

c.1467T>C · rs142398161 · VCV1487072

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00112%, nfe)

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 2.7, phastCons 1
Overall
CADD	14.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% European (non-Finnish) · 10/894,737 alleles

Filtering AF 0.000565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.000827% 10/1,209,636 alleles · very rare exomes 6/1,097,541 · genomes 4/112,095 · 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.Ser489=
Coding: c.1467T>C
MANE Select: NM_000276
dbSNP: rs142398161
Type: single nucleotide variant
Location: chrX:129569264 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 489: the 5-ppase domain; a β-strand

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

Disease context

Nephrolithiasis/nephrocalcinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Dent disease type 2 oculocerebrorenal syndrome

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-ser489 (accessed [today's date]).

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