Is OCRL p.Tyr425= (c.1275T>C) pathogenic?

OCRL p.Tyr425= (c.1275T>C) is classified Likely benign in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-25). Very rare (popmax 0.00296%, eas); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Tyr425= (c.1275T>C)?

OCRL p.Tyr425= (c.1275T>C) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Tyr425= (c.1275T>C) in the general population?

OCRL p.Tyr425= (c.1275T>C) is very rare (popmax 0.00296%, eas) (gnomAD).

OCRL p.Tyr425=

c.1275T>C · rs778559574 · VCV1766507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00296%, eas)

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 -0.75	GERP -5.3, phastCons 0.017
Overall
CADD	3.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00296% East Asian · 1/33,747 alleles

Filtering AF 0.000474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000343%

Overall 0.00108% 13/1,207,459 alleles · very rare exomes 12/1,095,408 · genomes 1/112,051 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00421%	23,760
East Asiangrpmax	0.00296%	33,747
African / African-American	0.00175%	57,132
European (non-Finnish)	0.00101%	99,218

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr425=
Coding: c.1275T>C
MANE Select: NM_000276
dbSNP: rs778559574
Type: single nucleotide variant
Location: chrX:129565802 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 425: the 5-ppase domain

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-tyr425 (accessed [today's date]).

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