Is CSPP1 p.Arg1114Cys (c.3340C>T) pathogenic?

CSPP1 p.Arg1114Cys (c.3340C>T) is classified Uncertain significance in CSPP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-11). Rare (popmax 0.151%, sas); Associated with Joubert syndrome 21.

What condition is associated with CSPP1 p.Arg1114Cys (c.3340C>T)?

CSPP1 p.Arg1114Cys (c.3340C>T) is associated with Joubert syndrome 21 (ClinVar).

How common is CSPP1 p.Arg1114Cys (c.3340C>T) in the general population?

CSPP1 p.Arg1114Cys (c.3340C>T) is rare (popmax 0.151%, sas) (gnomAD).

CSPP1 p.Arg1114Cys

c.3340C>T · rs537833447 · VCV1361696

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.151%, sas)

Conditions

Joubert syndrome 21

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.1	GERP 0.077
Regional constraint	o/e 0.96	unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic
Overall
CADD	15.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.151% South Asian · 137/90,898 alleles

Filtering AF 0.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00912% 147/1,612,354 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.151%	663
Remaining individualsnot grpmax-eligible	0.00641%	15,608
African / African-American	0.00267%	37,503
European (non-Finnish)	0.000339%	294,680

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.Arg1114Cys
Coding: c.3340C>T
MANE Select: NM_006421 · reported on NM_001382391
dbSNP: rs537833447
Type: single nucleotide variant
Location: chr8:67193473 (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-arg1114cys (accessed [today's date]).

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