HLCS p.Pro528fs
c.1581del · VCV4734847
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
holocarboxylase synthetase deficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 5 of 11 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- HLCS
- Protein
- p.Pro528fs
- Coding
- c.1581del
- MANE Select
- NM_001352514
- Type
- Deletion
- Location
- chr21:36930290 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.33
- Residue 528
- the bpl/lpl catalytic domain
Disease context
holocarboxylase synthetase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Holocarboxylase synthetase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 1 000 000 (Europe)
Similar variants
- HLCS c.2114_2121+5del Likely pathogenic ★★ same condition
- HLCS p.Arg648fs Likely pathogenic ★★ same condition
- HLCS p.Asp544fs Pathogenic/Likely pathogenic ★★ same condition
- HLCS p.Gln378fs Pathogenic/Likely pathogenic ★★ same condition
- HLCS p.Gln403_Val404insTer Pathogenic/Likely pathogenic ★★ same condition
- HLCS p.Gly408fs Pathogenic ★★ same condition
- HLCS p.Gly519fs Pathogenic/Likely pathogenic ★★ same condition
- HLCS p.His553fs Pathogenic/Likely pathogenic ★★ same condition
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/hlcs-p-pro528fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown