CLPP p.Tyr229=
c.687C>T · rs113472530 · VCV2902153
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0103%, nfe)
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 5.8 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 12.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0103%
European (non-Finnish) · 122/1,180,038 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00828%
Overall
0.00805%
130/1,614,052 alleles · ultra-rare
exomes 120/1,461,826 · genomes 10/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0103% | 9,672 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| African / African-American | 0.004% | 24,982 |
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.Tyr229=
- Coding
- c.687C>T
- MANE Select
- NM_006012
- dbSNP
- rs113472530
- Type
- single nucleotide variant
- Location
- chr19:6368563 (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 229
- a UniProt-annotated variant site (in prlts3); a β-strand
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-tyr229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown