Is HPD p.Phe98= (c.294C>T) pathogenic?

HPD p.Phe98= (c.294C>T) is classified Conflicting classifications of pathogenicity in HPD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-05-01). Rare (popmax 0.125%, amr); Associated with hawkinsinuria.

What condition is associated with HPD p.Phe98= (c.294C>T)?

HPD p.Phe98= (c.294C>T) is associated with hawkinsinuria, tyrosinemia type III (ClinVar).

How common is HPD p.Phe98= (c.294C>T) in the general population?

HPD p.Phe98= (c.294C>T) is rare (popmax 0.125%, amr) (gnomAD).

How is Hawkinsinuria inherited?

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

HPD p.Phe98=

c.294C>T · rs117079110 · VCV307487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.125%, amr)

Conditions

hawkinsinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3	GERP -3.8
Overall
CADD	3.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% Admixed American · 75/59,996 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0938%

Overall 0.0725% 1,170/1,614,054 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.125%	800
European (non-Finnish)	0.0871%	1,148
Remaining individualsnot grpmax-eligible	0.0672%	1,488
African / African-American	0.024%	4,167
Finnishnot grpmax-eligible	0.00625%	16,008
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,882
South Asian	0.0011%	91,082

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.Phe98=
Coding: c.294C>T
dbSNP: rs117079110
Type: single nucleotide variant
Location: chr12:121856354 (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-p-phe98 (accessed [today's date]).

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