CSPP1 p.Pro592=
c.1776G>A · rs201940935 · VCV1563758
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0825%, mid)
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 2.5 | GERP -0.91, phastCons 1 |
| Overall | ||
| CADD | 12.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0825%
Middle Eastern · 5/6,060 alleles
Filtering AF
0.0324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00409%
66/1,613,734 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0825% | 1,212 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| European (non-Finnish) | 0.0039% | 25,648 |
| African / African-American | 0.00267% | 37,508 |
| South Asian | 0.0022% | 45,502 |
| Admixed American | 0.00167% | 59,974 |
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.Pro592=
- Coding
- c.1776G>A
- MANE Select
- NM_001382391
- dbSNP
- rs201940935
- Type
- single nucleotide variant
- Location
- chr8:67132029 (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.Pro592Arg Uncertain significance ★★ same residue
- CSPP1 p.Pro592Leu 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
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-pro592 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown