Is HSD3B7 p.Phe342fs (c.1025del) pathogenic?

HSD3B7 p.Phe342fs (c.1025del) is classified Likely pathogenic in HSD3B7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-24). Very rare (popmax 0.00834%, amr); Associated with congenital bile acid synthesis defect 1.

What condition is associated with HSD3B7 p.Phe342fs (c.1025del)?

HSD3B7 p.Phe342fs (c.1025del) is associated with congenital bile acid synthesis defect 1 (ClinVar).

How common is HSD3B7 p.Phe342fs (c.1025del) in the general population?

HSD3B7 p.Phe342fs (c.1025del) is very rare (popmax 0.00834%, amr) (gnomAD).

How is Congenital bile acid synthesis defect type 1 inherited?

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

HSD3B7 p.Phe342fs

c.1025del · rs775934717 · VCV2628801

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

congenital bile acid synthesis defect 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,952 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000623% 10/1,605,776 alleles · very rare exomes 8/1,453,614 · genomes 2/152,162 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,990
Remaining individualsnot grpmax-eligible	0.0016%	62,350
European (non-Finnish)	0.000339%	294,618

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: HSD3B7
Protein: p.Phe342fs
Coding: c.1025del
MANE Select: NM_025193
dbSNP: rs775934717
Type: Deletion
Location: chr16:30988096 (GRCh38)
Gene constraint: LOEUF 1.411 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.01

Full HSD3B7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital bile acid synthesis defect 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital bile acid synthesis defect type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

HSD3B7 p.Gly17fs Pathogenic ★★ same condition
HSD3B7 c.694+2del Pathogenic ★ same condition
HSD3B7 p.Leu184fs Likely pathogenic ★ same condition
HSD3B7 p.Leu347fs Pathogenic ★ same condition
HSD3B7 p.Thr250fs Likely pathogenic ★ same condition
HSD3B7 p.Glu147Lys Pathogenic/Likely pathogenic ★★ same condition
HSD3B7 p.Glu167Ter Pathogenic/Likely pathogenic ★★ same condition
HSD3B7 p.Lys99fs 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/hsd3b7-p-phe342fs (accessed [today's date]).

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