Is OCRL p.Ser143fs (c.428_429del) pathogenic?

OCRL p.Ser143fs (c.428429del) is classified Likely pathogenic in OCRL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). Associated with OCRL-related disorder.

What condition is associated with OCRL p.Ser143fs (c.428_429del)?

OCRL p.Ser143fs (c.428_429del) is associated with OCRL-related disorder (ClinVar).

OCRL p.Ser143fs

c.428_429del · VCV4952751

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

OCRL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 6 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.36, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: OCRL
Protein: p.Ser143fs
Coding: c.428_429del
MANE Select: NM_000276
Type: Deletion
Location: chrX:129557938 (GRCh38)
Structure: AlphaFold pLDDT 82.91 · 5 PDB

Full OCRL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

OCRL-related disorder

Similar variants

OCRL p.Glu585del Pathogenic/Likely pathogenic ★★ same condition
OCRL p.Gln87fs Pathogenic ★ same condition
OCRL p.Gly726fs Likely pathogenic ★ same condition
OCRL p.Ser143Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
OCRL p.Ser143Pro Uncertain significance ★ same residue
OCRL p.Arg334Ter Pathogenic ★★ same condition
OCRL p.Arg500Gln Pathogenic ★★ same condition
OCRL p.Arg663Ter 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-ser143fs (accessed [today's date]).

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