CSPP1 c.99+304C>A
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 11.9%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +304 | deep intronic (+304 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -0.97 |
| Non-coding constraint | Z 0.91 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 6.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.9%
African / African-American · 4,946/41,444 alleles
Filtering AF
11.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.5%
Overall
3.47%
5,278/152,042 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.9% | 8 |
| Remaining individualsnot grpmax-eligible | 2.8% | 36 |
| Admixed American | 1.45% | 69 |
| Ashkenazi Jewishnot grpmax-eligible | 0.346% | 289 |
| South Asian | 0.0622% | 1,607 |
| European (non-Finnish) | 0.0544% | 1,837 |
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
- Coding
- c.99+304C>A
- MANE Select
- NM_001382391
- dbSNP
- rs6983995
- Type
- single nucleotide variant
- Location
- chr8:67074655 (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 type
- CSPP1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same type
- CSPP1 c.1497-2A>C Likely pathogenic ★★ same type
- CSPP1 c.1697+1G>T Pathogenic/Likely pathogenic ★★ same type
- CSPP1 c.2968+1G>A Pathogenic ★★ same type
- CSPP1 c.2968+1G>T Pathogenic ★★ same type
- CSPP1 c.923+1G>C Pathogenic ★★ same type
- CSPP1 c.-69C>T Pathogenic/Likely pathogenic ★★ same type
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-c-99-plus-304c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown