ALPL p.Pro261=
c.783G>A · rs537483743 · VCV1101467
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00533%, afr)
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 -8 | GERP -2.6 |
| Overall | ||
| CADD | 1.328 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00533%
African / African-American · 4/75,026 alleles
Filtering AF
0.00174%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000743%
12/1,614,088 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00533% | 18,756 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| East Asian | 0.00223% | 44,866 |
| Admixed American | 0.00167% | 60,018 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.000169% | 590,002 |
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.Pro261=
- Coding
- c.783G>A
- MANE Select
- NM_000478
- dbSNP
- rs537483743
- Type
- single nucleotide variant
- Location
- chr1:21568238 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.74 · 5 PDB
Similar variants
- ALPL p.Pro261Gln Uncertain significance ★★ ⚠ same residue
- ALPL p.Pro261Thr Uncertain significance ★★ ⚠ same residue
- ALPL p.Pro261Ser Likely pathogenic ★ ⚠ same residue
- ALPL p.Pro261Leu 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-pro261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown