ALPL p.Asn190Ter
c.567_568insT · VCV4086819
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Rare
Conditions
1
hypophosphatasia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 6 of 12 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -0.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ALPL
- Protein
- p.Asn190Ter
- Coding
- c.567_568insT
- MANE Select
- NM_000478
- Type
- Insertion
- Location
- chr1:21564135 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 190
- an α-helix; a disulfide bond
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.Asn190del Pathogenic/Likely pathogenic ★★ same residue
- ALPL p.Leu512fs Pathogenic/Likely pathogenic ★★ same condition
- ALPL p.Met226fs Pathogenic/Likely pathogenic ★★ same condition
- ALPL p.Tyr101fs Pathogenic/Likely pathogenic ★★ same condition
- ALPL p.Val217fs Pathogenic ★★ same condition
- ALPL p.Ala485fs Likely pathogenic ★ same condition
- ALPL p.Asn303fs Likely pathogenic ★ same condition
- ALPL p.Asn190Lys Uncertain significance ★ ⚠ same residue
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-asn190ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown