Is CSPP1 p.Pro1095= (c.3285C>T) pathogenic?

CSPP1 p.Pro1095= (c.3285C>T) is classified Benign/Likely benign in CSPP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Rare (popmax 0.525%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Pro1095= (c.3285C>T)?

CSPP1 p.Pro1095= (c.3285C>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Pro1095= (c.3285C>T) in the general population?

CSPP1 p.Pro1095= (c.3285C>T) is rare (popmax 0.525%, afr) (gnomAD).

CSPP1 p.Pro1095=

c.3285C>T · rs201008264 · VCV380774

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.525%, 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 -0.94	GERP -4.2, phastCons 0.001
Overall
CADD	4.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.525% African / African-American · 394/75,016 alleles

Filtering AF 0.482% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.466%

Overall 0.0309% 498/1,614,100 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.525%	190
Admixed American	0.0833%	1,200
Remaining individualsnot grpmax-eligible	0.0496%	2,016
South Asian	0.011%	9,108
European (non-Finnish)	0.0011%	90,767

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.Pro1095=
Coding: c.3285C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs201008264
Type: single nucleotide variant
Location: chr8:67190714 (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-pro1095 (accessed [today's date]).

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