Is HPD p.Thr2= (c.6G>A) pathogenic?

HPD p.Thr2= (c.6G>A) is classified Likely benign in HPD (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-19). Very rare (popmax 0.00167%, amr); Associated with hawkinsinuria.

What condition is associated with HPD p.Thr2= (c.6G>A)?

HPD p.Thr2= (c.6G>A) is associated with hawkinsinuria, tyrosinemia type III (ClinVar).

How common is HPD p.Thr2= (c.6G>A) in the general population?

HPD p.Thr2= (c.6G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Hawkinsinuria inherited?

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

HPD p.Thr2=

c.6G>A · rs377475703 · VCV2932256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

hawkinsinuria

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -13	GERP -3.9
Overall
CADD	2.853	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00124% 20/1,614,062 alleles · very rare exomes 17/1,461,814 · genomes 3/152,248 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Finnishnot grpmax-eligible	0.00156%	64,034
European (non-Finnish)	0.00136%	73,748
African / African-American	0.00133%	75,016
South Asian	0.0011%	91,060

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.Thr2=
Coding: c.6G>A
MANE Select: NM_002150
dbSNP: rs377475703
Type: single nucleotide variant
Location: chr12:121858711 (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-thr2 (accessed [today's date]).

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