Is CSPP1 c.2128+36del pathogenic?

CSPP1 c.2128+36del is classified Benign/Likely benign in CSPP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Common (popmax 61.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 21.

What condition is associated with CSPP1 c.2128+36del?

CSPP1 c.2128+36del is associated with Joubert syndrome 21 (ClinVar).

CSPP1 c.2128+36del

Q: How common is CSPP1 c.2128+36del in the general population?

CSPP1 c.2128+36del is common (popmax 61.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs11296619 · VCV402568

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 61.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +36	near-intronic (+36 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -2.3, phastCons 0.53
Overall
CADD	1.194	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(T)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 61.7% African / African-American · 27,594/44,748 alleles

Filtering AF 61.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.8%

Overall 40% 449,087/1,122,134 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	90.2%	1
African / African-Americangrpmax	61.7%	2
Ashkenazi Jewishnot grpmax-eligible	40.9%	2
European (non-Finnish)	40.4%	2
Admixed American	40.2%	2
Remaining individualsnot grpmax-eligible	37.1%	3
Middle Eastern	35.1%	3
East Asian	34.7%	3
South Asian	30.3%	3
Finnishnot grpmax-eligible	24.8%	4

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.2128+36del
MANE Select: NM_001382391
dbSNP: rs11296619
Type: Deletion
Location: chr8:67149948 (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-c-2128-plus-36del (accessed [today's date]).

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