ALG1 c.390+46T>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 4.11%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +46 | near-intronic (+46 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.2 | GERP 0.098 |
| Overall | ||
| CADD | 3.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.11%
African / African-American · 3,035/73,862 alleles
Filtering AF
3.99%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.94%
Overall
0.237%
3,707/1,562,406 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.11% | 24 |
| Middle Eastern | 0.452% | 221 |
| Remaining individualsnot grpmax-eligible | 0.351% | 285 |
| Admixed American | 0.317% | 315 |
| European (non-Finnish) | 0.0213% | 4,689 |
| South Asian | 0.00446% | 22,429 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,252 |
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
- Coding
- c.390+46T>A
- MANE Select
- NM_019109
- dbSNP
- rs111714766
- Type
- single nucleotide variant
- Location
- chr16:5073302 (GRCh38)
- Gene constraint
- LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.24
Similar variants
- ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALG1 c.1187+2T>C Pathogenic ★★ same type
- ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same type
- ALG1 c.209-2A>G Likely pathogenic ★★ same type
- ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same type
- ALG1 c.630-2A>G Likely pathogenic ★★ same type
- ALG1 c.863-2A>G Likely pathogenic ★★ same type
- ALG1 c.961+1G>A 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/alg1-c-390-plus-46t-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown