HSD17B4 p.Leu730=
c.2190T>C · rs1580736426 · VCV794253
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Perrault syndrome
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 -0.8 | GERP -3.7, phastCons 0.019 |
| Overall | ||
| CADD | 2.561 | 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
- HSD17B4
- Protein
- p.Leu730=
- Coding
- c.2190T>C
- MANE Select
- NM_000414
- dbSNP
- rs1580736426
- Type
- single nucleotide variant
- Location
- chr5:119541973 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.65 · 7 PDB
- Residue 730
- an α-helix; the scp2 domain
Disease context
Perrault syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: d-bifunctional protein deficiency
For Perrault syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood
Similar variants
- HSD17B4 c.1210-1G>A Pathogenic/Likely pathogenic ★★ same condition
- HSD17B4 c.1262-1G>A Likely pathogenic ★★ same condition
- HSD17B4 c.1438-1G>A Pathogenic/Likely pathogenic ★★ same condition
- HSD17B4 c.1503+1G>A Likely pathogenic ★★ same condition
- HSD17B4 c.1573+1G>A Likely pathogenic ★★ same condition
- HSD17B4 c.1574-1G>A Likely pathogenic ★★ same condition
- HSD17B4 c.1768-1G>A Pathogenic/Likely pathogenic ★★ same condition
- HSD17B4 c.1993+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/hsd17b4-p-leu730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown