Is CSPP1 p.Ile48fs (c.140dup) pathogenic?

CSPP1 p.Ile48fs (c.140dup) is classified Pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). Absent from gnomAD; Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Ile48fs (c.140dup)?

CSPP1 p.Ile48fs (c.140dup) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Ile48fs (c.140dup) in the general population?

CSPP1 p.Ile48fs (c.140dup) is absent from gnomAD (gnomAD).

CSPP1 p.Ile48fs

c.140dup · rs2488286486 · VCV2803716

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.085	GERP -3.5, phastCons 0.18

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: CSPP1
Protein: p.Ile48fs
Coding: c.140dup
MANE Select: NM_001382391
dbSNP: rs2488286486
Type: Duplication
Location: chr8:67076521 (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 p.Glu843fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Lys45Ter Pathogenic ★★ same condition
CSPP1 p.Tyr273Ter Pathogenic ★★ same condition
CSPP1 c.1023-7dup Benign/Likely benign ★★ same condition
CSPP1 c.1288-12dup Benign/Likely benign ★★ same condition
CSPP1 c.200-5dup Benign/Likely benign ★★ same condition
CSPP1 c.-10-5dup Benign/Likely benign ★★ same condition
CSPP1 p.Ile454fs 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-ile48fs (accessed [today's date]).

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