ALPL p.Pro194=
c.582T>C · rs112063292 · VCV1115861
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0293%, afr)
Conditions
3
adult hypophosphatasia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.9 |
| Overall | ||
| CADD | 0.732 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0293%
African / African-American · 22/75,034 alleles
Filtering AF
0.0198%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.00167%
27/1,614,034 alleles · ultra-rare
exomes 25/1,461,792 · genomes 2/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0293% | 3,411 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| Admixed American | 0.00167% | 60,016 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- ALPL
- Protein
- p.Pro194=
- Coding
- c.582T>C
- MANE Select
- NM_000478
- dbSNP
- rs112063292
- Type
- single nucleotide variant
- Location
- chr1:21564150 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 194
- an α-helix
Similar variants
- ALPL p.Pro194fs Pathogenic/Likely pathogenic ★★ same residue
- ALPL p.Pro194Arg Uncertain significance ★ ⚠ 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
- ALPL c.649-1G>A Pathogenic/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/alpl-p-pro194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown