SIX1 p.Ser284=
c.852C>T · rs772202186 · VCV2921458
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
2
branchiootic syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 10.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,086 alleles
Overall
6.2e-05%
1/1,612,044 alleles · very rare
exomes 1/1,459,760 · genomes 0/152,284 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SIX1
- Protein
- p.Ser284=
- Coding
- c.852C>T
- MANE Select
- NM_005982
- dbSNP
- rs772202186
- Type
- single nucleotide variant
- Location
- chr14:60646286 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.87 · 1 PDB
Similar variants
- SIX1 p.Arg110Gln Pathogenic/Likely pathogenic ★★ same condition
- SIX1 p.Arg110Trp Pathogenic ★★ same condition
- SIX1 p.Glu125Lys Pathogenic/Likely pathogenic ★★ same condition
- SIX1 p.Tyr129Cys Pathogenic ★★ same condition
- SIX1 p.Val106Met Likely pathogenic ★★ same condition
- SIX1 p.Ala184Thr Uncertain significance ★★ same condition
- SIX1 p.Arg119His Uncertain significance ★★ ⚠ same condition
- SIX1 p.Arg140Gln 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/six1-p-ser284 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown