Is CSPP1 p.Leu503fs (c.1507del) pathogenic?

CSPP1 p.Leu503fs (c.1507del) is classified Pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Leu503fs (c.1507del)?

CSPP1 p.Leu503fs (c.1507del) is associated with Joubert syndrome 21 (ClinVar).

CSPP1 p.Leu503fs

c.1507del · VCV4688585

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.46, phastCons 1

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

Variant & gene context

Gene: CSPP1
Protein: p.Leu503fs
Coding: c.1507del
MANE Select: NM_001382391
Type: Deletion
Location: chr8:67118258 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 57.34

Full CSPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 21 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSPP1 c.-54_-51del Likely pathogenic ★★ same condition
CSPP1 p.Asn908fs Pathogenic ★★ same condition
CSPP1 p.Gln753fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Glu11fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Glu755fs Pathogenic ★★ same condition
CSPP1 p.Glu89fs Pathogenic ★★ same condition
CSPP1 p.His85fs Pathogenic ★★ same condition
CSPP1 p.Ile841fs 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/cspp1-p-leu503fs (accessed [today's date]).

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