CLPP c.270+161A>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 77.7%, 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 +161 | deep intronic (+161 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -1.7 |
| Overall | ||
| CADD | 1.486 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
77.7%
African / African-American · 38,935/50,124 alleles
Filtering AF
77%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 76.8%
Overall
22.5%
125,122/557,248 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 77.7% | 1 |
| East Asian | 41.3% | 2 |
| South Asian | 31.9% | 3 |
| Admixed American | 24.2% | 4 |
| Remaining individualsnot grpmax-eligible | 20.4% | 5 |
| Middle Eastern | 19.1% | 5 |
| Finnishnot grpmax-eligible | 14.8% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 12.5% | 8 |
| European (non-Finnish) | 11.7% | 9 |
| Amishnot grpmax-eligible | 10.6% | 9 |
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
- CLPP
- Coding
- c.270+161A>C
- MANE Select
- NM_006012
- dbSNP
- rs10416820
- Type
- single nucleotide variant
- Location
- chr19:6362101 (GRCh38)
- Gene constraint
- LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.68 · 32 PDB
Similar variants
- CLPP c.368-2A>G Pathogenic/Likely pathogenic ★★ same type
- CLPP p.Ala10Gly Uncertain significance ★★ ⚠ same type
- CLPP p.Ala10Ser Uncertain significance ★★ ⚠ same type
- CLPP p.Ala128Thr Uncertain significance ★★ ⚠ same type
- CLPP p.Ala223Thr Uncertain significance ★★ ⚠ same type
- CLPP p.Ala43Thr Uncertain significance ★★ ⚠ same type
- CLPP p.Ala50Thr Uncertain significance ★★ ⚠ same type
- CLPP p.Arg174Cys Uncertain significance ★★ ⚠ 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/clpp-c-270-plus-161a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown