CLPP p.Ile220=
c.660C>T · VCV3371870
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0268%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -5 |
| Overall | ||
| CADD | 8.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0268%
East Asian · 12/44,766 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00131%
21/1,604,386 alleles · ultra-rare
exomes 16/1,452,120 · genomes 5/152,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0268% | 3,730 |
| African / African-American | 0.00267% | 37,430 |
| European (non-Finnish) | 0.000597% | 167,600 |
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
- Protein
- p.Ile220=
- Coding
- c.660C>T
- MANE Select
- NM_006012
- Type
- single nucleotide variant
- Location
- chr19:6366362 (GRCh38)
- Gene constraint
- LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.68 · 32 PDB
- Residue 220
- an α-helix
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-p-ile220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown