ALPL p.His482fs
c.1444dup · rs2545351182 · VCV2665004
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 8 | GERP 1.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ALPL
- Protein
- p.His482fs
- Coding
- c.1444dup
- MANE Select
- NM_000478
- dbSNP
- rs2545351182
- Type
- Duplication
- Location
- chr1:21577512 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 482
- an α-helix
Disease context
hypophosphatasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hypophosphatasia (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
Similar variants
- ALPL p.His482Asn Pathogenic/Likely pathogenic ★★ same residue
- ALPL p.His482= Likely benign ★★ same residue
- ALPL p.His482Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- ALPL p.His482Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
- ALPL p.Arg391fs Pathogenic/Likely pathogenic ★★ same condition
- ALPL p.Gln361fs Pathogenic ★★ same condition
- ALPL p.Gly222fs Pathogenic/Likely pathogenic ★★ same condition
- ALPL p.His340fs 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/alpl-p-his482fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown