Is CSPP1 p.Ter1227= (c.*3_*6dup) pathogenic?

CSPP1 p.Ter1227= (c.36dup) is classified Uncertain significance in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-11). Very rare (popmax 0.000678%, nfe); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Ter1227= (c.*3_*6dup)?

CSPP1 p.Ter1227= (c.*3_*6dup) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Ter1227= (c.*3_*6dup) in the general population?

CSPP1 p.Ter1227= (c.*3_*6dup) is very rare (popmax 0.000678%, nfe) (gnomAD).

CSPP1 p.Ter1227=

c.*3_*6dup · rs764952763 · VCV1024615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Joubert syndrome 21

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.9	GERP -1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,658 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,686 alleles · very rare exomes 8/1,461,348 · genomes 0/152,338 · joint denominator

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.Ter1227=
Coding: c.*3_*6dup
MANE Select: NM_001382391
dbSNP: rs764952763
Type: Duplication
Location: chr8:67195592 (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-ter1227 (accessed [today's date]).

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