CSPP1 p.Phe533=
c.1599C>T · rs1343187773 · VCV2415046
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
Joubert syndrome 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.8 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 14.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,988 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000372%
6/1,613,392 alleles · very rare
exomes 4/1,461,320 · genomes 2/152,072 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,994 |
| South Asian | 0.0022% | 45,531 |
| African / African-American | 0.00134% | 74,868 |
| European (non-Finnish) | 8.48e-05% | 1,179,567 |
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.Phe533=
- Coding
- c.1599C>T
- MANE Select
- NM_001382391
- dbSNP
- rs1343187773
- Type
- single nucleotide variant
- Location
- chr8:67118350 (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-phe533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown