CSPP1 p.Ala406Val
c.1217C>T · rs775268714 · VCV1329767
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0113%, eas)
Conditions
1
Joubert syndrome 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.12 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing |
| Pangolin | Δ0.21 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 25.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0113%
East Asian · 5/44,334 alleles
Filtering AF
0.00439%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.000755%
12/1,589,860 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0113% | 8,867 |
| Admixed American | 0.00347% | 28,781 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,494 |
| African / African-American | 0.00135% | 74,140 |
| South Asian | 0.00113% | 88,566 |
| European (non-Finnish) | 0.000172% | 581,974 |
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.Ala406Val
- Coding
- c.1217C>T
- MANE Select
- NM_001382391
- dbSNP
- rs775268714
- Type
- single nucleotide variant
- Location
- chr8:67113834 (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.Ala406= Likely benign ★★ 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-ala406val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown