GLS p.Phe224fs
c.671_681del · VCV3364564
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
global developmental delay, progressive ataxia, and elevated glutamine
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function; NMD-escape possible for C-terminal truncations |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.43 | GERP -1.6, phastCons 0.99 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GLS
- Protein
- p.Phe224fs
- Coding
- c.671_681del
- MANE Select
- NM_014905
- Type
- Deletion
- Location
- chr2:190900628 (GRCh38)
- Structure
- AlphaFold pLDDT 85.66 · 4 PDB
- Residue 224
- an α-helix
Similar variants
- GLS2 p.Leu224Pro Uncertain significance ★ ⚠ same residue
- GLS p.Tyr308Ter Pathogenic ★ same condition
- GLS p.Trp63Cys Uncertain significance ★ ⚠ same condition
- GLS p.Pro313Leu Pathogenic same condition
- GLS c.1131-11del Likely benign ★ 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/gls-p-phe224fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown