Is HGD p.Pro103fs (c.308_317del) pathogenic?

HGD p.Pro103fs (c.308317del) is classified Likely pathogenic in HGD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). Associated with alkaptonuria.

What condition is associated with HGD p.Pro103fs (c.308_317del)?

HGD p.Pro103fs (c.308_317del) is associated with alkaptonuria (ClinVar).

How is Alkaptonuria inherited?

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

HGD p.Pro103fs

c.308_317del · VCV3588286

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

alkaptonuria

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 5 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 0.63, phastCons 1

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

Variant & gene context

Gene: HGD
Protein: p.Pro103fs
Coding: c.308_317del
MANE Select: NM_000187
Type: Deletion
Location: chr3:120652617 (GRCh38)
Gene constraint: LOEUF 1.199 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.85 · 2 PDB
Residue 103: an α-helix

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

Disease context

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

For Alkaptonuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

HGD p.Pro103Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
HGD p.Arg197fs Pathogenic ★★ same condition
HGD p.Ser59fs Pathogenic ★★ same condition
HGD c.283-5del Benign/Likely benign ★★ same condition
HGD c.413_434+35del Pathogenic ★ same condition
HGD c.434+1del Pathogenic ★ same condition
HGD c.652del Pathogenic ★ same condition
HGD p.Arg225fs 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/hgd-p-pro103fs (accessed [today's date]).

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