ALPL p.Ala468=
c.1404G>A · rs774384124 · VCV256228
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00932%, 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 -15 | GERP -3.6 |
| Overall | ||
| CADD | 0.264 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00932%
European (non-Finnish) · 110/1,179,926 alleles
Filtering AF
0.00791%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00736%
Overall
0.00702%
113/1,610,036 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00932% | 10,727 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,223 |
| South Asian | 0.0011% | 91,088 |
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.Ala468=
- Coding
- c.1404G>A
- MANE Select
- NM_000478
- dbSNP
- rs774384124
- Type
- single nucleotide variant
- Location
- chr1:21577477 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
- Residue 468
- a UniProt-annotated variant site (in hops); an α-helix
Similar variants
- ALPL p.Ala468Ser Likely pathogenic ★★ ⚠ same residue
- ALPL p.Ala468Thr Pathogenic/Likely pathogenic ★★ same residue
- ALPL p.Ala468Val Pathogenic/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
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-ala468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown