Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.2%, amr) — 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 +80 | deep intronic (+80 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.49 | GERP 0.52, phastCons 0.16 |
| Non-coding constraint | Z 1.80 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 8.471 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2%
Admixed American · 3,500/56,444 alleles
Filtering AF
6.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.96%
Overall
4.95%
66,973/1,353,330 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 6.2% | 16 |
| European (non-Finnish) | 5.87% | 17 |
| Ashkenazi Jewishnot grpmax-eligible | 5.58% | 18 |
| Remaining individualsnot grpmax-eligible | 4.34% | 23 |
| Amishnot grpmax-eligible | 4.18% | 24 |
| Finnishnot grpmax-eligible | 3.25% | 31 |
| Middle Eastern | 1.88% | 53 |
| South Asian | 1.03% | 97 |
| African / African-American | 0.96% | 104 |
| East Asian | 0.00691% | 14,462 |
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
- CPS1
- Coding
- c.4002+80T>C
- MANE Select
- NM_001875
- dbSNP
- rs7567836
- Type
- single nucleotide variant
- Location
- chr2:210663277 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.80 · 14 PDB
Similar variants
- CPS1 c.1086+1G>A Likely pathogenic ★★ same type
- CPS1 c.1087-1G>T Pathogenic/Likely pathogenic ★★ same type
- CPS1 c.1165-2A>G Likely pathogenic ★★ same type
- CPS1 c.1263+5G>C Pathogenic/Likely pathogenic ★★ same type
- CPS1 c.1549+1G>A Pathogenic/Likely pathogenic ★★ same type
- CPS1 c.1549+1G>T Pathogenic/Likely pathogenic ★★ same type
- CPS1 c.1837-8A>G Pathogenic/Likely pathogenic ★★ same type
- CPS1 c.1981+1G>C 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/cps1-c-4002-plus-80t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown