Is HPD c.324+8A>G pathogenic?

HPD c.324+8A>G is classified Likely benign in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-18). Absent from gnomAD v4.1; Associated with hawkinsinuria.

What condition is associated with HPD c.324+8A>G?

HPD c.324+8A>G is associated with hawkinsinuria, tyrosinemia type III (ClinVar).

How common is HPD c.324+8A>G in the general population?

HPD c.324+8A>G is absent from gnomAD v4.1 (gnomAD).

How is Hawkinsinuria inherited?

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

HPD c.324+8A>G

rs2137630925 · VCV1108049

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hawkinsinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +8	near-intronic (+8 nt from the splice site)
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.8	GERP -3.6
Non-coding constraint	Z 1.48	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HPD
Coding: c.324+8A>G
dbSNP: rs2137630925
Type: single nucleotide variant
Location: chr12:121856316 (GRCh38)

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

Disease context

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

Also linked: tyrosinemia type III

For Hawkinsinuria (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

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-c-324-plus-8a-g (accessed [today's date]).

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