Is HSD17B4 p.Ser385= (c.1155T>C) pathogenic?

HSD17B4 p.Ser385= (c.1155T>C) is classified Likely benign in HSD17B4 (ClinVar, Single submitter, 3 submitters; last evaluated 2023-08-14). Ultra-rare (popmax 0.0329%, mid); Associated with d-bifunctional protein deficiency.

What condition is associated with HSD17B4 p.Ser385= (c.1155T>C)?

HSD17B4 p.Ser385= (c.1155T>C) is associated with d-bifunctional protein deficiency, Perrault syndrome (ClinVar).

How common is HSD17B4 p.Ser385= (c.1155T>C) in the general population?

HSD17B4 p.Ser385= (c.1155T>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Bifunctional enzyme deficiency inherited?

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

HSD17B4 p.Ser385=

c.1155T>C · rs370055428 · VCV1109045

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

d-bifunctional protein 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 -0.059	GERP -2.7
Overall
CADD	1.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,082 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00118% 19/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,041
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.00127%	78,653

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: HSD17B4
Protein: p.Ser385=
Coding: c.1155T>C
MANE Select: NM_000414
dbSNP: rs370055428
Type: single nucleotide variant
Location: chr5:119499499 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.65 · 7 PDB
Residue 385: an α-helix; the 'enoyl-coa hydratase 2' region

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

Disease context

d-bifunctional protein deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Perrault syndrome

For Bifunctional enzyme deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

HSD17B4 p.Ser385Tyr Uncertain significance ★★ ⚠ 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-ser385 (accessed [today's date]).

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