ALG1 p.Glu275=
c.825G>A · rs754552258 · VCV3030863
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
Conditions
1
ALG1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 0.36, phastCons 1 |
| Overall | ||
| CADD | 9.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/90,982 alleles
Filtering AF
0.000876%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00112%
18/1,611,982 alleles · very rare
exomes 18/1,459,650 · genomes 0/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,327 |
| European (non-Finnish) | 0.00127% | 78,651 |
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
- ALG1
- Protein
- p.Glu275=
- Coding
- c.825G>A
- MANE Select
- NM_019109
- dbSNP
- rs754552258
- Type
- single nucleotide variant
- Location
- chr16:5078841 (GRCh38)
- Gene constraint
- LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.24
Disease context
ALG1-related disorder
Similar variants
- ALG1 p.Glu275Ter Pathogenic/Likely pathogenic ★★ same residue
- ALG1 p.Glu275Gln Uncertain significance ★ ⚠ same residue
- ALG1 p.Ser258Leu Pathogenic/Likely pathogenic ★★ same condition
- ALG1 p.Tyr113Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG1 p.Arg247His Likely pathogenic ★ ⚠ same condition
- ALG1 c.1187+3A>G Conflicting classifications of pathogenicity ★ same condition
- ALG1 c.*5T>C Likely benign same condition
- ALG1 p.Cys390= Likely benign same condition
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/alg1-p-glu275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown