HPD p.Phe206=
c.618C>T · rs2500299043 · VCV2940068
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
hawkinsinuria
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 2.8 | GERP -0.78, phastCons 1 |
| Overall | ||
| CADD | 10.84 | 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
- Protein
- p.Phe206=
- Coding
- c.618C>T
- MANE Select
- NM_002150
- dbSNP
- rs2500299043
- Type
- single nucleotide variant
- Location
- chr12:121847193 (GRCh38)
- Gene constraint
- LOEUF 0.845 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.00 · 4 PDB
- Residue 206
- a UniProt-annotated variant site (in tyrsn3; likely pathogenic); the voc 2 domain
Disease context
hawkinsinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: tyrosinemia type III
For Hawkinsinuria (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
- Prevalence
- <1 / 1 000 000 (Worldwide)
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-phe206 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown