ALG8 p.Glu452Ter
c.1354G>T · VCV3574028
Likely pathogenic
Multiple submitters
Classification
Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
polycystic liver disease 3 with or without kidney cysts
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| REVEL | 0.33 | indeterminate |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 46.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ALG8
- Protein
- p.Glu452Ter
- Coding
- c.1354G>T
- MANE Select
- NM_024079
- Type
- single nucleotide variant
- Location
- chr11:78101191 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07
- Residue 452
- a UniProt-annotated variant site (in pcld3)
Similar variants
- ALG8 p.Glu452= Likely benign ★ same residue
- ALG8 p.Glu452fs Pathogenic ★ same residue
- 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
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-glu452ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown