SIX1 p.Pro249fs
c.746del · VCV4921909
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4.5 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SIX1
- Protein
- p.Pro249fs
- Coding
- c.746del
- MANE Select
- NM_005982
- Type
- Deletion
- Location
- chr14:60646392 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.87 · 1 PDB
- Residue 249
- a UniProt-annotated variant site (in bor; uncertain significance); the 'disordered' region
Similar variants
- SIX1 p.Pro249Gln Benign/Likely benign ★★ same residue
- SIX1 p.Pro249Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- SIX1 p.Glu133del Pathogenic/Likely pathogenic ★★ same type
- SIX1 c.561-34_561-31del Benign/Likely benign ★★ same type
- SIX1 p.Gly107fs Likely pathogenic ★ same type
- SIX1 p.Tyr129_Cys130del Likely pathogenic ★ same type
- SIX1 c.561-4_598del Uncertain significance ★ same type
- SIX1 p.Ala105_Gly107del Uncertain significance ★ 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/six1-p-pro249fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown