Is CSPP1 p.Thr1215= (c.3645T>G) pathogenic?

CSPP1 p.Thr1215= (c.3645T>G) is classified Likely benign in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-15). Ultra-rare (popmax 0.0167%, amr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Thr1215= (c.3645T>G)?

CSPP1 p.Thr1215= (c.3645T>G) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Thr1215= (c.3645T>G) in the general population?

CSPP1 p.Thr1215= (c.3645T>G) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

CSPP1 p.Thr1215=

c.3645T>G · rs749332092 · VCV1594491

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

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
Pangolin	Δ0.73	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -0.045	GERP -3.4
Overall
CADD	5.204	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/60,008 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00062% 10/1,614,090 alleles · ultra-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.Thr1215=
Coding: c.3645T>G
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs749332092
Type: single nucleotide variant
Location: chr8:67195557 (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-thr1215 (accessed [today's date]).

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