Is HPD p.Asp102= (c.306T>C) pathogenic?

HPD p.Asp102= (c.306T>C) is classified Likely benign in HPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). Very rare (popmax 0.00133%, afr); Associated with tyrosinemia type III.

What condition is associated with HPD p.Asp102= (c.306T>C)?

HPD p.Asp102= (c.306T>C) is associated with tyrosinemia type III, hawkinsinuria (ClinVar).

How common is HPD p.Asp102= (c.306T>C) in the general population?

HPD p.Asp102= (c.306T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Tyrosinemia type 3 inherited?

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

HPD p.Asp102=

c.306T>C · VCV3753533

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

tyrosinemia type III

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.8
Overall
CADD	6.585	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,984 alleles

Overall 6.84e-05% 1/1,461,780 alleles · very 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
Protein: p.Asp102=
Coding: c.306T>C
MANE Select: NM_002150
Type: single nucleotide variant
Location: chr12:121856342 (GRCh38)
Gene constraint: LOEUF 0.845 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 4 PDB
Residue 102: the voc 1 domain

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

Also linked: hawkinsinuria

For Tyrosinemia type 3 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

HPD p.Arg225Ter Pathogenic/Likely pathogenic ★★ same condition
HPD p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
HPD p.Tyr160Cys Likely pathogenic ★★ same condition
HPD p.Ala230Thr Uncertain significance ★★ ⚠ same condition
HPD p.Arg111Trp Uncertain significance ★★ ⚠ same condition
HPD p.Arg119Gln Uncertain significance ★★ ⚠ same condition
HPD p.Arg279Gly Uncertain significance ★★ ⚠ same condition
HPD p.Arg300Trp 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-asp102 (accessed [today's date]).

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