HPD p.Gln31Ter
c.91C>T · rs2500329137 · VCV2128171
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 14 |
| Splicing | ||
| SpliceAI | Δ0.95 | donor gain · deltas |
| Pangolin | Δ0.82 | gain · loss 0.76 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 62.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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.Gln31Ter
- Coding
- c.91C>T
- MANE Select
- NM_002150
- dbSNP
- rs2500329137
- Type
- single nucleotide variant
- Location
- chr12:121857759 (GRCh38)
- Gene constraint
- LOEUF 0.845 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.00 · 4 PDB
- Residue 31
- the voc 1 domain; an α-helix
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 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-gln31ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown