CSPP1 p.Arg308Lys
c.923G>A · rs2129545557 · VCV1401558
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.97e-05%, 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 | 0.183 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.86 | donor loss · deltas |
| Pangolin | Δ0.76 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.97e-05%
European (non-Finnish) · 1/1,115,316 alleles
Overall
7.34e-05%
1/1,362,854 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.Arg308Lys
- Coding
- c.923G>A
- MANE Select
- NM_001382391
- dbSNP
- rs2129545557
- Type
- single nucleotide variant
- Location
- chr8:67095732 (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 p.Arg308Gly Uncertain significance ★ same residue
- 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
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-arg308lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown