SETBP1 p.Ser477Ter
c.1430C>G · VCV4938855
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
SETBP1-related disorder
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 haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 6 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.9 | GERP 2.7, phastCons 0.98 |
| Overall | ||
| CADD | 35.0 | 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
- SETBP1
- Protein
- p.Ser477Ter
- Coding
- c.1430C>G
- MANE Select
- NM_015559
- Type
- single nucleotide variant
- Location
- chr18:44950770 (GRCh38)
- Gene constraint
- LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 43.30
- Residue 477
- the 'disordered' region
Disease context
SETBP1-related disorder
Similar variants
- SETBP1 p.Arg544Ter Pathogenic/Likely pathogenic ★★ same condition
- SETBP1 p.Arg626Ter Pathogenic ★★ same condition
- SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same condition
- SETBP1 p.Ser867Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SETBP1 p.Lys664Glu Uncertain significance ★★ ⚠ same condition
- SETBP1 p.Gln712Ter Pathogenic ★ same condition
- SETBP1 p.Pro855Ser Likely pathogenic ★ ⚠ same condition
- SETBP1 p.Ser869Asn Pathogenic ★ 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/setbp1-p-ser477ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown