Is OCRL p.Lys701Arg (c.2102A>G) pathogenic?

OCRL p.Lys701Arg (c.2102A>G) is classified Uncertain significance in OCRL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-20). AlphaMissense: likely benign (0.0752); Very rare (popmax 0.00125%, nfe); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Lys701Arg (c.2102A>G)?

OCRL p.Lys701Arg (c.2102A>G) is associated with Nephrolithiasis/nephrocalcinosis, Dent disease type 2, oculocerebrorenal syndrome (ClinVar).

How common is OCRL p.Lys701Arg (c.2102A>G) in the general population?

OCRL p.Lys701Arg (c.2102A>G) is very rare (popmax 0.00125%, nfe) (gnomAD).

What do computational predictors say about OCRL p.Lys701Arg (c.2102A>G)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

OCRL p.Lys701Arg

c.2102A>G · VCV3598024

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00125%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.78	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 9.3	GERP 2.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00125% European (non-Finnish) · 11/880,627 alleles

Filtering AF 0.00067% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00049%

Overall 0.000921% 11/1,193,904 alleles · very rare exomes 10/1,081,545 · genomes 1/112,359 · 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.Lys701Arg
Coding: c.2102A>G
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129576539 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 701: a turn

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-lys701arg (accessed [today's date]).

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