CSPP1 p.Pro1165Ser
c.3493C>T · rs200161440 · VCV383716
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.64%, mid)
Conditions
1
Joubert syndrome 21
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not looked up on this page · why |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 2, phastCons 0.88 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 121 kb · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 19.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.64%
Middle Eastern · 99/6,024 alleles
Filtering AF
1.38%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.28%
Overall
0.0903%
1,458/1,613,936 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.64% | 61 |
| Ashkenazi Jewishnot grpmax-eligible | 1.44% | 69 |
| Admixed American | 0.282% | 355 |
| Remaining individualsnot grpmax-eligible | 0.245% | 409 |
| African / African-American | 0.0653% | 1,531 |
| European (non-Finnish) | 0.0453% | 2,205 |
| South Asian | 0.0253% | 3,959 |
| East Asian | 0.00668% | 14,963 |
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.Pro1165Ser
- Coding
- c.3493C>T
- MANE Select
- NM_006421 · reported on NM_001382391
- dbSNP
- rs200161440
- Type
- single nucleotide variant
- Location
- chr8:67195405 (GRCh38)
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-pro1165ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown