Is CSPP1 p.Arg994Ter (c.2980C>T) pathogenic?

CSPP1 p.Arg994Ter (c.2980C>T) is classified Pathogenic in CSPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). Very rare (popmax 0.00134%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg994Ter (c.2980C>T)?

CSPP1 p.Arg994Ter (c.2980C>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg994Ter (c.2980C>T) in the general population?

CSPP1 p.Arg994Ter (c.2980C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CSPP1 p.Arg994Ter

c.2980C>T · rs760275528 · VCV1069030

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 0.00134%, 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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 1.4, phastCons 1
Overall
CADD	38.0	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 0.00134% African / African-American · 1/74,728 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000549% 8/1,456,880 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,280
African / African-Americangrpmax	0.00134%	74,728
South Asian	0.0011%	90,500
European (non-Finnish)	0.000425%	235,460

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg994Ter
Coding: c.2980C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs760275528
Type: single nucleotide variant
Location: chr8:67175307 (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-arg994ter (accessed [today's date]).

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