Is CSPP1 p.Tyr273Ter (c.818dup) pathogenic?

CSPP1 p.Tyr273Ter (c.818dup) is classified Pathogenic in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-06). Very rare (popmax 0.00133%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Tyr273Ter (c.818dup)?

CSPP1 p.Tyr273Ter (c.818dup) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Tyr273Ter (c.818dup) in the general population?

CSPP1 p.Tyr273Ter (c.818dup) is very rare (popmax 0.00133%, afr) (gnomAD).

CSPP1 p.Tyr273Ter

c.818dup · VCV3710105

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.32	GERP -0.82

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,032 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 10/1,461,300 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,032
European (non-Finnish)	0.000763%	131,067

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.Tyr273Ter
Coding: c.818dup
MANE Select: NM_001382391
Type: Duplication
Location: chr8:67095626 (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 p.Tyr273Cys Uncertain significance ★ same residue
CSPP1 p.Glu843fs Pathogenic/Likely pathogenic ★★ same condition
CSPP1 p.Lys45Ter Pathogenic ★★ same condition
CSPP1 c.1023-7dup Benign/Likely benign ★★ same condition
CSPP1 c.1288-12dup Benign/Likely benign ★★ same condition
CSPP1 c.200-5dup Benign/Likely benign ★★ same condition
CSPP1 c.-10-5dup Benign/Likely benign ★★ same condition
CSPP1 p.Ile454fs 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-p-tyr273ter (accessed [today's date]).

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