PLCB4 p.Arg640fs
c.1918del · VCV4082118
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
familial hypercholesterolemia
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 24 of 40 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PLCB4
- Protein
- p.Arg640fs
- Coding
- c.1918del
- MANE Select
- NM_001377142
- Type
- Deletion
- Location
- chr20:9409099 (GRCh38)
- Gene constraint
- LOEUF 0.509 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 86.03
- Residue 640
- the pi-plc y-box domain
Similar variants
- PLCB4 p.Arg640Gln Uncertain significance ★★ ⚠ same residue
- PLCB4 p.Glu1011fs Pathogenic ★ same type
- PLCB4 p.Ile272fs Likely pathogenic ★ same type
- PLCB4 p.Phe7fs Likely pathogenic ★ same type
- PLCB4 p.Lys1078fs Uncertain significance ★ same type
- PLCB4 c.2525-8del Benign ★ same type
- PLCB4 c.3409-27del Benign ★ same type
- PLCB4 c.3409-6_3409-5del 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/plcb4-p-arg640fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown