Is HSD17B4 p.Val97= (c.291C>A) pathogenic?

HSD17B4 p.Val97= (c.291C>A) is classified Likely benign in HSD17B4 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-09). No allele count reported in gnomAD v4.1 (AN 1,598,104); Associated with Perrault syndrome.

What condition is associated with HSD17B4 p.Val97= (c.291C>A)?

HSD17B4 p.Val97= (c.291C>A) is associated with Perrault syndrome, d-bifunctional protein deficiency (ClinVar).

How common is HSD17B4 p.Val97= (c.291C>A) in the general population?

HSD17B4 p.Val97= (c.291C>A) is no allele count reported in gnomAD v4.1 (AN 1,598,104) (gnomAD).

How is Perrault syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HSD17B4 p.Val97=

c.291C>A · rs2531609498 · VCV2943291

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,104)

Conditions

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 1.2	GERP -1.9, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,104). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HSD17B4
Protein: p.Val97=
Coding: c.291C>A
MANE Select: NM_000414
dbSNP: rs2531609498
Type: single nucleotide variant
Location: chr5:119475716 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.65 · 7 PDB
Residue 97: the '(3r)-hydroxyacyl-coa dehydrogenase' region; a β-strand

Full HSD17B4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Perrault syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: d-bifunctional protein deficiency

For Perrault syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

HSD17B4 p.Val97fs Likely pathogenic ★ same residue
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

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-val97 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown