CLPP p.Asp251=
c.753C>T · rs747747764 · VCV1587821
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0122%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -4.5 |
| Overall | ||
| CADD | 0.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0122%
South Asian · 11/90,474 alleles
Filtering AF
0.00681%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00525%
Overall
0.00161%
26/1,611,070 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0122% | 8,225 |
| African / African-American | 0.00401% | 24,957 |
| Admixed American | 0.00336% | 29,786 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,396 |
| European (non-Finnish) | 0.000764% | 130,975 |
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.Asp251=
- Coding
- c.753C>T
- MANE Select
- NM_006012
- dbSNP
- rs747747764
- Type
- single nucleotide variant
- Location
- chr19:6368629 (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 251
- the 'disordered' region
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-asp251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown