ALPL p.Ile490=
c.1470C>T · rs771120248 · VCV811483
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
2
Inborn genetic diseases
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 -7.6 | GERP -3.6 |
| Overall | ||
| CADD | 2.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00283%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00252%
Overall
0.00324%
52/1,606,022 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,608 |
| European (non-Finnish) | 0.00373% | 26,815 |
| Admixed American | 0.00333% | 30,001 |
| African / African-American | 0.00133% | 74,932 |
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.Ile490=
- Coding
- c.1470C>T
- MANE Select
- NM_000478
- dbSNP
- rs771120248
- Type
- single nucleotide variant
- Location
- chr1:21577543 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 490
- a UniProt-annotated variant site (in hops; odonto; partial loss of activity); a disulfide bond
Similar variants
- ALPL p.Ile490Phe Likely pathogenic ★★ ⚠ same residue
- ALPL p.Ile490Leu Uncertain significance ★ ⚠ same residue
- ALPL c.1190-2A>T Pathogenic ★★ same condition
- ALPL c.182-1G>A Pathogenic/Likely pathogenic ★★ same condition
- ALPL c.182-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ALPL c.297+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ALPL c.298-1G>A Pathogenic ★★ same condition
- ALPL c.472+1G>A 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-ile490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown