ALG8 p.Ser404=
c.1212G>A · rs200575151 · VCV3032354
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
ALG8-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.046 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4.2 |
| Overall | ||
| CADD | 0.396 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.00198%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00169%
Overall
0.00213%
34/1,596,242 alleles · ultra-rare
exomes 32/1,444,108 · genomes 2/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| European (non-Finnish) | 0.00273% | 36,598 |
| East Asian | 0.00224% | 44,570 |
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
- Protein
- p.Ser404=
- Coding
- c.1212G>A
- MANE Select
- NM_024079
- dbSNP
- rs200575151
- Type
- single nucleotide variant
- Location
- chr11:78104420 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07
- Residue 404
- a UniProt-annotated variant site (in pcld3)
Disease context
ALG8-related disorder
Similar variants
- ALG8 p.Ser404Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- ALG8 c.777+1G>A Likely pathogenic ★★ same condition
- ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
- ALG8 p.Pro425Gln Uncertain significance ★★ ⚠ same condition
- ALG8 p.Tyr463Cys Uncertain significance ★ ⚠ same condition
- ALG8 c.898+1G>T Likely pathogenic same condition
- ALG8 p.Phe143Cys Uncertain significance ⚠ 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-p-ser404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown