Is CSPP1 p.Arg1142= (c.3426A>G) pathogenic?

CSPP1 p.Arg1142= (c.3426A>G) is classified Likely benign in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-05). Very rare (popmax 0.00549%, sas); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1142= (c.3426A>G)?

CSPP1 p.Arg1142= (c.3426A>G) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1142= (c.3426A>G) in the general population?

CSPP1 p.Arg1142= (c.3426A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

CSPP1 p.Arg1142=

c.3426A>G · VCV4765716

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP -1.8, phastCons 1
Overall
CADD	6.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,082 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000434% 7/1,613,820 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
European (non-Finnish)	0.00017%	589,904

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.Arg1142=
Coding: c.3426A>G
MANE Select: NM_006421 · reported on NM_001382391
Type: single nucleotide variant
Location: chr8:67193559 (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-arg1142 (accessed [today's date]).

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