SIX3 p.Cys96Ter
c.288T>A · rs1553337648 · VCV489225
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
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 1 of 2 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.033 | GERP -1.4, phastCons 0.74 |
| Overall | ||
| CADD | 38.0 | 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
- SIX3
- Protein
- p.Cys96Ter
- Coding
- c.288T>A
- MANE Select
- NM_005413
- dbSNP
- rs1553337648
- Type
- single nucleotide variant
- Location
- chr2:44942392 (GRCh38)
- Gene constraint
- LOEUF 0.387 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38
- Residue 96
- the 'interaction with tle5' region
Similar variants
- SIX3 p.Ala72Val Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg146Cys Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg201His Uncertain significance ★★ ⚠ same type
- SIX3 p.Arg281Ser Uncertain significance ★★ same type
- SIX3 p.Asp205His Uncertain significance ★★ ⚠ same type
- SIX3 p.Gly103Arg Uncertain significance ★★ ⚠ same type
- SIX3 p.Gly244Cys Uncertain significance ★★ ⚠ same type
- SIX3 p.Gly317Ser 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/six3-p-cys96ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown