Is OCRL p.Arg337His (c.1010G>A) pathogenic?

OCRL p.Arg337His (c.1010G>A) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.00217%, amr); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Arg337His (c.1010G>A)?

OCRL p.Arg337His (c.1010G>A) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Arg337His (c.1010G>A) in the general population?

OCRL p.Arg337His (c.1010G>A) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about OCRL p.Arg337His (c.1010G>A)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

OCRL p.Arg337His

c.1010G>A · VCV4615856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -7.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.8	GERP 1, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	22.9	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 0.00217% Admixed American · 1/46,014 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000496% 6/1,210,109 alleles · very rare exomes 6/1,096,453 · genomes 0/113,656 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00217%	46,014
South Asian	0.00175%	56,982
European (non-Finnish)	0.000447%	223,483

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.Arg337His
Coding: c.1010G>A
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129562454 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 337: a UniProt-annotated variant site (in ocrl; associated in cis with i-361); a UniProt-annotated variant site (in ocrl); 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

Similar variants

OCRL p.Arg337Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-arg337his (accessed [today's date]).

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