CYFIP2 p.Arg514Ter
c.1540C>T · rs868243549 · VCV1028474
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
developmental and epileptic encephalopathy, 65
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 in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 15 of 31 |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing |
| Pangolin | Δ0.39 | loss · gain 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 47.0 | 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
- CYFIP2
- Protein
- p.Arg514Ter
- Coding
- c.1540C>T
- MANE Select
- NM_001037333
- dbSNP
- rs868243549
- Type
- single nucleotide variant
- Location
- chr5:157320671 (GRCh38)
- Gene constraint
- LOEUF 0.274 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.28
Similar variants
- CYFIP2 p.Arg514Gln Uncertain significance ★ ⚠ same residue
- CYFIP2 p.Arg514= Likely benign ★ same residue
- CYFIP2 p.Arg87Cys Pathogenic/Likely pathogenic ★★ same condition
- CYFIP2 p.Arg87Pro Pathogenic/Likely pathogenic ★★ same condition
- CYFIP2 p.Glu640Lys Pathogenic ★★ same condition
- CYFIP2 p.Tyr108His Likely pathogenic ★★ ⚠ same condition
- CYFIP2 p.Arg1045Trp Uncertain significance ★★ ⚠ same condition
- CYFIP2 p.Arg353Trp 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/cyfip2-p-arg514ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown