ALG8 p.Trp230Ter
c.689G>A · VCV4038361
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 13 |
| REVEL | 0.277 | benign-leaning |
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss · deltas |
| Pangolin | Δ0.36 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 51.0 | 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.Trp230Ter
- Coding
- c.689G>A
- MANE Select
- NM_024079
- Type
- single nucleotide variant
- Location
- chr11:78113974 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.07
- Residue 230
- a UniProt-annotated variant site (in pcld3)
Similar variants
- ALG8 p.Ala250Val Uncertain significance ★★ ⚠ same condition
- ALG8 p.Ala388Pro Uncertain significance ★★ ⚠ same condition
- ALG8 p.Ala403Thr Uncertain significance ★★ ⚠ same condition
- ALG8 p.Ala424Val Uncertain significance ★★ ⚠ same condition
- ALG8 p.Ala72Val Uncertain significance ★★ ⚠ same condition
- ALG8 p.Arg215Gln Uncertain significance ★★ ⚠ same condition
- ALG8 p.Gly130Glu Uncertain significance ★★ ⚠ same condition
- ALG8 p.Ile144Phe 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-trp230ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown