CSPP1 p.Leu16=
c.46T>C · rs150924296 · VCV681050
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.889%, eas)
Conditions
1
Joubert syndrome 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.79 | GERP -3.4 |
| Overall | ||
| CADD | 2.935 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.889%
East Asian · 398/44,758 alleles
Filtering AF
0.817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.789%
Overall
0.0336%
542/1,611,816 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.889% | 112 |
| Ashkenazi Jewishnot grpmax-eligible | 0.115% | 869 |
| Remaining individualsnot grpmax-eligible | 0.0465% | 2,151 |
| South Asian | 0.0453% | 2,208 |
| African / African-American | 0.004% | 24,984 |
| European (non-Finnish) | 0.00314% | 31,866 |
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.Leu16=
- Coding
- c.46T>C
- MANE Select
- NM_001382391
- dbSNP
- rs150924296
- Type
- single nucleotide variant
- Location
- chr8:67074298 (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.Leu16Val 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-leu16 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown