Is OCRL p.Leu448Ser (c.1343T>C) pathogenic?

OCRL p.Leu448Ser (c.1343T>C) is classified Uncertain significance in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.5448); No allele count reported in gnomAD v4.1 (AN 1,184,989); Associated with Nephrolithiasis/nephrocalcinosis.

What condition is associated with OCRL p.Leu448Ser (c.1343T>C)?

OCRL p.Leu448Ser (c.1343T>C) is associated with Nephrolithiasis/nephrocalcinosis (ClinVar).

How common is OCRL p.Leu448Ser (c.1343T>C) in the general population?

OCRL p.Leu448Ser (c.1343T>C) is no allele count reported in gnomAD v4.1 (AN 1,184,989) (gnomAD).

What do computational predictors say about OCRL p.Leu448Ser (c.1343T>C)?

AlphaMissense predicts ambiguous (score 0.5448) — an in-silico prediction, not a clinical call.

OCRL p.Leu448Ser

c.1343T>C · VCV3923812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5448 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,184,989)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Nephrolithiasis/nephrocalcinosis

Computational evidence

Protein change
AlphaMissense	0.5448	ambiguous
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -9.72	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 31 kb · p 4.7e-26 · regional, not allelic
Overall
CADD	24.2	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

No allele count reported in gnomAD v4.1 (AN 1,184,989). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: OCRL
Protein: p.Leu448Ser
Coding: c.1343T>C
MANE Select: NM_000276
Type: single nucleotide variant
Location: chrX:129565870 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB
Residue 448: the 5-ppase domain; an α-helix

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-leu448ser (accessed [today's date]).

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