ALPL p.Ala399=
c.1197C>T · rs764010876 · VCV1114154
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00559%, nfe)
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 -0.68 | GERP -0.54, phastCons 0.01 |
| Overall | ||
| CADD | 8.393 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00559%
European (non-Finnish) · 66/1,179,900 alleles
Filtering AF
0.00451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00411%
Overall
0.0044%
71/1,613,764 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00559% | 17,877 |
| Finnishnot grpmax-eligible | 0.00469% | 21,333 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| African / African-American | 0.00134% | 74,876 |
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.Ala399=
- Coding
- c.1197C>T
- MANE Select
- NM_000478
- dbSNP
- rs764010876
- Type
- single nucleotide variant
- Location
- chr1:21576529 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 399
- a UniProt-annotated variant site (in hops)
Similar variants
- ALPL p.Ala399Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
- ALPL p.Ala399Val Likely pathogenic ★★ ⚠ same residue
- ALPL p.Ala399Pro Uncertain significance ★ ⚠ same residue
- ALPL p.Ala399Thr Conflicting classifications of pathogenicity ★ ⚠ 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
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-ala399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown