Is CSPP1 p.Val1132del (c.3395_3397del) pathogenic?

CSPP1 p.Val1132del (c.33953397del) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). Ultra-rare (popmax 0.04%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Val1132del (c.3395_3397del)?

CSPP1 p.Val1132del (c.3395_3397del) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Val1132del (c.3395_3397del) in the general population?

CSPP1 p.Val1132del (c.3395_3397del) is ultra-rare (popmax 0.04%, afr) (gnomAD).

CSPP1 p.Val1132del

c.3395_3397del · rs749558548 · VCV426386

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.1	GERP 0.5, phastCons 1
Overall
CADD	11.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% African / African-American · 30/75,052 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00223% 36/1,612,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,502
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Val1132del
Coding: c.3395_3397del
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs749558548
Type: Deletion
Location: chr8:67193526 (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-val1132del (accessed [today's date]).

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