Is CSPP1 p.Arg1144Ter (c.3430C>T) pathogenic?

CSPP1 p.Arg1144Ter (c.3430C>T) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-12). Ultra-rare (popmax 0.0233%, amr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1144Ter (c.3430C>T)?

CSPP1 p.Arg1144Ter (c.3430C>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1144Ter (c.3430C>T) in the general population?

CSPP1 p.Arg1144Ter (c.3430C>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

CSPP1 p.Arg1144Ter

c.3430C>T · rs200346372 · VCV1418605

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

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
Constraint at this position
Conservation	phyloP 0.35	GERP 0.05, phastCons 0.98
Overall
CADD	36.0	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 0.0233% Admixed American · 14/59,992 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.00167% 27/1,613,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,285
Remaining individualsnot grpmax-eligible	0.0016%	62,446
South Asian	0.0011%	91,056
European (non-Finnish)	0.000933%	107,220

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.Arg1144Ter
Coding: c.3430C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs200346372
Type: single nucleotide variant
Location: chr8:67193563 (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-arg1144ter (accessed [today's date]).

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