GLB1 p.Lys356=
c.1068G>A · rs794726980 · VCV193584
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.41 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,782 alleles
Overall
6.2e-05%
1/1,612,570 alleles · very rare
exomes 1/1,460,322 · genomes 0/152,248 · joint denominator
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
- GLB1
- Protein
- p.Lys356=
- Coding
- c.1068G>A
- MANE Select
- NM_000404
- dbSNP
- rs794726980
- Type
- single nucleotide variant
- Location
- chr3:33046120 (GRCh38)
- Gene constraint
- LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.19 · 8 PDB
Similar variants
- TMPPE p.Glu356Gln Uncertain significance ★ ⚠ same residue
- GLB1 c.1144-2A>G Pathogenic/Likely pathogenic ★★ same type
- GLB1 c.1233+1G>A Pathogenic/Likely pathogenic ★★ same type
- GLB1 c.1347+1G>T Likely pathogenic ★★ same type
- GLB1 c.1479+1G>A Pathogenic ★★ same type
- GLB1 c.1480-1G>C Pathogenic/Likely pathogenic ★★ same type
- GLB1 c.1480-2A>G Pathogenic ★★ same type
- GLB1 c.245+1G>A 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/glb1-p-lys356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown