Is HPD c.3+11del pathogenic?

HPD c.3+11del is classified Likely benign in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). Ultra-rare (popmax 0.0133%, afr); Associated with hawkinsinuria.

What condition is associated with HPD c.3+11del?

HPD c.3+11del is associated with hawkinsinuria, tyrosinemia type III (ClinVar).

How common is HPD c.3+11del in the general population?

HPD c.3+11del is ultra-rare (popmax 0.0133%, afr) (gnomAD).

How is Hawkinsinuria inherited?

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

HPD c.3+11del

rs778977403 · VCV2927506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

hawkinsinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +11	near-intronic (+11 nt from the splice site)
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.9	GERP 0.5
Non-coding constraint	Z 2.60	1 kb window · o/e 0.80 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/75,038 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.000684% 10/1,461,850 alleles · ultra-rare

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: HPD
Coding: c.3+11del
dbSNP: rs778977403
Type: Deletion
Location: chr12:121858810 (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-3-plus-11del (accessed [today's date]).

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