Is HPD p.Gln155fs (c.463del) pathogenic?

HPD p.Gln155fs (c.463del) is classified Pathogenic in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-03). Absent from gnomAD; Associated with tyrosinemia type III.

What condition is associated with HPD p.Gln155fs (c.463del)?

HPD p.Gln155fs (c.463del) is associated with tyrosinemia type III (ClinVar).

How common is HPD p.Gln155fs (c.463del) in the general population?

HPD p.Gln155fs (c.463del) is absent from gnomAD (gnomAD).

How is Tyrosinemia type 3 inherited?

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

HPD p.Gln155fs

c.463del · rs2137619413 · VCV1333313

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

tyrosinemia type III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.81	GERP -1.7

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: HPD
Protein: p.Gln155fs
Coding: c.463del
MANE Select: NM_002150
dbSNP: rs2137619413
Type: Deletion
Location: chr12:121849742 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 4 PDB
Residue 155: a β-strand

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

Disease context

tyrosinemia type III — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tyrosinemia type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

HPD p.Arg48fs Pathogenic ★ same condition
HPD p.Glu179fs Pathogenic ★ same condition
HPD p.Gly49fs Pathogenic ★ same condition
HPD p.Ile240fs Likely pathogenic ★ same condition
HPD p.Leu289fs Pathogenic ★ same condition
HPD p.Pro239fs Pathogenic ★ same condition
HPD c.31-33_31-11del Uncertain significance ★ same condition
HPD p.Arg119_Glu120delinsGln Uncertain significance ★ 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/hpd-p-gln155fs (accessed [today's date]).

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