Is OCRL p.Pro495Ser (c.1483C>T) pathogenic?

OCRL p.Pro495Ser (c.1483C>T) is classified Likely pathogenic in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-04). AlphaMissense: likely pathogenic (0.9957); Absent from gnomAD v4.1; Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Pro495Ser (c.1483C>T)?

OCRL p.Pro495Ser (c.1483C>T) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Pro495Ser (c.1483C>T) in the general population?

OCRL p.Pro495Ser (c.1483C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about OCRL p.Pro495Ser (c.1483C>T)?

AlphaMissense predicts likely pathogenic (score 0.9957) — an in-silico prediction, not a clinical call.

OCRL p.Pro495Ser

c.1483C>T · VCV4839706

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9957 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.9957	likely pathogenic ✓ concordant with ClinVar · top 6% in OCRL
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -14.33	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: OCRL
Protein: p.Pro495Ser
Coding: c.1483C>T
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129569280 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 495: an α-helix; the 5-ppase domain; a UniProt-annotated variant site (in ocrl)

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

Similar variants

OCRL p.Arg25Pro Uncertain significance ★★ ⚠ same condition
OCRL p.Arg457His Uncertain significance ★★ ⚠ same condition
OCRL p.Asn196Thr Uncertain significance ★★ ⚠ same condition
OCRL p.Lys312Glu Uncertain significance ★★ ⚠ same condition
OCRL p.Lys701Arg Uncertain significance ★★ ⚠ same condition
OCRL p.Ser648Leu Uncertain significance ★★ ⚠ same condition
OCRL p.Val630Ala Uncertain significance ★★ ⚠ same condition
OCRL c.1602+11G>A Benign/Likely benign ★★ 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-pro495ser (accessed [today's date]).

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