ALG12 p.Leu159=
c.475C>T · rs1569176378 · VCV3030650
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Conditions
1
ALG12-related disorder
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 3.8 | GERP -2.5, phastCons 0.79 |
| Overall | ||
| CADD | 7.907 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,177,140 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000206%
3/1,454,206 alleles · very rare
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
- ALG12
- Protein
- p.Leu159=
- Coding
- c.475C>T
- MANE Select
- NM_024105
- dbSNP
- rs1569176378
- Type
- single nucleotide variant
- Location
- chr22:49910083 (GRCh38)
- Gene constraint
- LOEUF 0.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.26
Disease context
ALG12-related disorder
Similar variants
- ALG12 p.Leu159Arg Uncertain significance ★ ⚠ same residue
- ALG12 p.Arg146Gln Pathogenic/Likely pathogenic ★★ same condition
- ALG12 p.Gly101Arg Likely pathogenic ★★ same condition
- ALG12 p.Ser36Arg Uncertain significance ⚠ same condition
- ALG12 c.295+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALG12 c.768+1G>A Likely pathogenic ★★ same type
- ALG12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same type
- ALG12 p.Thr67Met 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/alg12-p-leu159 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown