Is CSPP1 p.Arg1048Gln (c.3143G>A) pathogenic?

CSPP1 p.Arg1048Gln (c.3143G>A) is classified Conflicting classifications of pathogenicity in CSPP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-01-04). Very rare (popmax 0.00134%, afr); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1048Gln (c.3143G>A)?

CSPP1 p.Arg1048Gln (c.3143G>A) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1048Gln (c.3143G>A) in the general population?

CSPP1 p.Arg1048Gln (c.3143G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

CSPP1 p.Arg1048Gln

c.3143G>A · rs371166744 · VCV2888195

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

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.
REVEL	0.007	strongly benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -6	GERP -5.4
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	2.135	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,850 alleles

Overall 0.000124% 2/1,611,352 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,850
European (non-Finnish)	8.49e-05%	1,178,008

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.Arg1048Gln
Coding: c.3143G>A
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs371166744
Type: single nucleotide variant
Location: chr8:67177713 (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-arg1048gln (accessed [today's date]).

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