Is CSPP1 p.Arg1136fs (c.3405_3406del) pathogenic?

CSPP1 p.Arg1136fs (c.34053406del) is classified Pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-19). Very rare (popmax 8.48e-05%, nfe); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1136fs (c.3405_3406del)?

CSPP1 p.Arg1136fs (c.3405_3406del) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1136fs (c.3405_3406del) in the general population?

CSPP1 p.Arg1136fs (c.3405_3406del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CSPP1 p.Arg1136fs

c.3405_3406del · rs2129575958 · VCV1445486

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,310 alleles

Overall 6.84e-05% 1/1,461,070 alleles · very rare

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: CSPP1
Protein: p.Arg1136fs
Coding: c.3405_3406del
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs2129575958
Type: Deletion
Location: chr8:67193538 (GRCh38)

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

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-arg1136fs (accessed [today's date]).

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