CSPP1 p.Arg130Ser
c.390G>T · rs370128733 · VCV2987736
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000599%, nfe)
Conditions
1
Joubert syndrome 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.222 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.42 | acceptor loss at this position · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 0.073 | GERP -3.5, phastCons 0.36 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 22.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000599%
European (non-Finnish) · 7/1,168,954 alleles
Filtering AF
0.000249%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00016%
Overall
0.000484%
7/1,445,932 alleles · very rare
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.Arg130Ser
- Coding
- c.390G>T
- MANE Select
- NM_001382391
- dbSNP
- rs370128733
- Type
- single nucleotide variant
- Location
- chr8:67093548 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 57.34
Similar variants
- CSPP1 c.1022+1G>T Likely pathogenic ★★ same condition
- CSPP1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CSPP1 c.1497-2A>C Likely pathogenic ★★ same condition
- CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same condition
- CSPP1 c.2968+1G>A Pathogenic ★★ same condition
- CSPP1 c.2968+1G>T Pathogenic ★★ same condition
- CSPP1 c.923+1G>C Pathogenic ★★ same condition
- CSPP1 c.-69C>T Pathogenic/Likely pathogenic ★★ same condition
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-arg130ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown