Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 100%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
1
ALG8-congenital disorder of glycosylation
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +35 | near-intronic (+35 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP -1.4, phastCons 0.96 |
| Overall | ||
| CADD | 7.585 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
Middle Eastern · 5,820/5,820 alleles
Filtering AF
99.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 99.8%
Overall
100%
1,494,179/1,494,184 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed American | 100% | 1 |
| East Asian | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| Middle Easterngrpmax | 100% | 1 |
| Remaining individualsnot grpmax-eligible | 100% | 1 |
| European (non-Finnish) | 100% | 1 |
| South Asian | 100% | 1 |
| Finnishnot grpmax-eligible | 100% | 1 |
| African / African-American | 100% | 1 |
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
- ALG8
- Coding
- c.478+35A>T
- MANE Select
- NM_024079
- dbSNP
- rs518624
- Type
- single nucleotide variant
- Location
- chr11:78121030 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07
Disease context
ALG8-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor ALG8-CDG (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Antenatal, Infancy, Neonatal
Similar variants
- ALG8 c.368+2T>G Likely pathogenic ★★ same condition
- ALG8 c.674-2A>G Likely pathogenic ★★ same condition
- ALG8 c.777+1G>A Likely pathogenic ★★ same condition
- ALG8 c.95+1G>A Likely pathogenic ★★ same condition
- ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG8 p.Arg364Ter Pathogenic/Likely pathogenic ★★ 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/alg8-c-478-plus-35a-t (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown