ALPL p.Arg152Ser
c.454C>A · VCV4856177
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3743 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
adult hypophosphatasia
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3743 | ambiguous |
|---|---|---|
| REVEL | 0.423 | indeterminate |
| SaProt | LLR -4.59 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.9, phastCons 1 |
| Regional constraint | o/e 0.83 | unconstrained · MANE · 24 kb · p 6.1e-06 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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
- ALPL
- Protein
- p.Arg152Ser
- Coding
- c.454C>A
- MANE Select
- NM_000478
- Type
- single nucleotide variant
- Location
- chr1:21563266 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 152
- an α-helix; a disulfide bond; a UniProt-annotated variant site (in hops; uncertain significance); a UniProt-annotated variant site (in hops; benign; lethal form)
Similar variants
- ALPL p.Arg152His Benign/Likely benign ★★ same residue
- ALPL p.Arg152= Conflicting classifications of pathogenicity ★ same residue
- ALPL p.Arg152Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
- ALPL c.1190-2A>T Pathogenic ★★ same condition
- ALPL c.298-1G>A Pathogenic ★★ same condition
- ALPL c.62-1G>C Pathogenic/Likely pathogenic ★★ same condition
- ALPL c.648+1G>A Pathogenic ★★ same condition
- ALPL c.648+1G>T 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-arg152ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown