HPD p.Val22fs
c.65_66del · VCV3753543
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
2
tyrosinemia type III
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 14 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- HPD
- Protein
- p.Val22fs
- Coding
- c.65_66del
- MANE Select
- NM_002150
- Type
- Microsatellite
- Location
- chr12:121857784 (GRCh38)
- Gene constraint
- LOEUF 0.845 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.00 · 4 PDB
- Residue 22
- the voc 1 domain; a β-strand
Disease context
tyrosinemia type III — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: hawkinsinuria
For Tyrosinemia type 3 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- HPD c.199-10_199-8del Likely benign ★★ same condition
- HPD p.Arg284fs Pathogenic ★ same condition
- HPD p.Gly285fs Pathogenic ★ same condition
- HPD c.1072-18_1072-16del Likely benign ★ same condition
- HPD c.1072-18CT[2] Likely benign ★ same condition
- HPD p.Arg225Ter Pathogenic/Likely pathogenic ★★ same condition
- HPD p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
- HPD p.Tyr160Cys Likely pathogenic ★★ 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-val22fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown