ALPL p.Val423=
c.1269G>C · rs1644740707 · VCV1992074
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
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 3.4 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 6.077 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,076 alleles
Overall
0.000124%
2/1,613,888 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,076 |
| European (non-Finnish) | 8.47e-05% | 1,179,967 |
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.Val423=
- Coding
- c.1269G>C
- MANE Select
- NM_000478
- dbSNP
- rs1644740707
- Type
- single nucleotide variant
- Location
- chr1:21576601 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 423
- a UniProt-annotated variant site (in hops; 16% alkaline of phosphatase activity); a β-strand
Similar variants
- ALPL p.Val423Ala Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ALPL p.Val423Met Likely pathogenic ★ ⚠ same residue
- ALPL c.1190-2A>T Pathogenic ★★ same type
- ALPL c.182-1G>A Pathogenic/Likely pathogenic ★★ same type
- ALPL c.182-2A>G Pathogenic/Likely pathogenic ★★ same type
- ALPL c.297+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALPL c.298-1G>A Pathogenic ★★ same type
- ALPL c.472+1G>A Pathogenic ★★ same type
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-val423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown