Is CSPP1 p.Arg1048Ter (c.3142C>T) pathogenic?

CSPP1 p.Arg1048Ter (c.3142C>T) is classified Pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Very rare (popmax 0.00893%, eas); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1048Ter (c.3142C>T)?

CSPP1 p.Arg1048Ter (c.3142C>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1048Ter (c.3142C>T) in the general population?

CSPP1 p.Arg1048Ter (c.3142C>T) is very rare (popmax 0.00893%, eas) (gnomAD).

CSPP1 p.Arg1048Ter

c.3142C>T · rs200881715 · VCV1322167

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.20	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 2	GERP -0.059, phastCons 0.006
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,802 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00137% 22/1,611,142 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,201
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,382
African / African-American	0.00133%	74,926
European (non-Finnish)	0.00119%	84,130

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.Arg1048Ter
Coding: c.3142C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs200881715
Type: single nucleotide variant
Location: chr8:67177712 (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-arg1048ter (accessed [today's date]).

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