HLCS p.Val730=
c.2190T>C · rs2089756578 · VCV1631873
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
holocarboxylase synthetase deficiency
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 0.42 | GERP -0.055, phastCons 0.76 |
| Overall | ||
| CADD | 6.773 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HLCS
- Protein
- p.Val730=
- Coding
- c.2190T>C
- MANE Select
- NM_001352514
- dbSNP
- rs2089756578
- Type
- single nucleotide variant
- Location
- chr21:36759773 (GRCh38)
- Gene constraint
- LOEUF 0.883 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.33
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.1620+2T>G Likely pathogenic ★★ same condition
- HLCS c.1621-2A>G Likely pathogenic ★★ same condition
- HLCS c.1892+1G>A Likely pathogenic ★★ same condition
- HLCS c.1960+5G>A Pathogenic ★★ same condition
- HLCS c.2121+1G>A Pathogenic/Likely pathogenic ★★ same condition
- HLCS c.2237-2A>G Likely pathogenic ★★ same condition
- HLCS c.2450+2T>A Likely pathogenic ★★ same condition
- HLCS c.2451-1G>A 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-val730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown