CSPP1 p.Thr659=
c.1977T>C · rs114177619 · VCV474852
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.71%, afr)
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 | all four deltas below 0.2 · T>A here scores Δ0.71 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 13.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.71%
African / African-American · 1,926/71,028 alleles
Filtering AF
2.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.57%
Overall
0.136%
2,094/1,534,256 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.71% | 37 |
| Remaining individualsnot grpmax-eligible | 0.157% | 638 |
| Admixed American | 0.134% | 747 |
| Middle Eastern | 0.0527% | 1,898 |
| South Asian | 0.00395% | 25,339 |
| East Asian | 0.00237% | 42,210 |
| European (non-Finnish) | 0.000785% | 127,371 |
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.Thr659=
- Coding
- c.1977T>C
- MANE Select
- NM_001382391
- dbSNP
- rs114177619
- Type
- single nucleotide variant
- Location
- chr8:67149784 (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.Thr659Ser 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-thr659 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown