PPCS c.508+18A>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +18 | near-intronic (+18 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not looked up on this page · why |
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -3 |
| Non-coding constraint | Z 0.73 | 1 kb window · o/e 0.95 · regional · uncalibrated |
| Overall | ||
| CADD | 3.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,218 alleles
Overall
0.000127%
2/1,580,756 alleles · very rare
exomes 1/1,428,676 · genomes 1/152,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00135% | 74,218 |
| European (non-Finnish) | 8.57e-05% | 1,166,952 |
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
- PPCS
- Coding
- c.508+18A>C
- MANE Select
- NM_024664
- Type
- single nucleotide variant
- Location
- chr1:42457091 (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/ppcs-c-508-plus-18a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown