SIX1 p.Ile69=
c.207C>T · rs1169502259 · VCV3075842
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
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 1.9 | GERP -0.74, phastCons 1 |
| Overall | ||
| CADD | 11.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,942 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000558%
9/1,614,088 alleles · very rare
exomes 5/1,461,868 · genomes 4/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,981 |
| Admixed American | 0.00167% | 60,012 |
| European (non-Finnish) | 0.000424% | 236,008 |
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.Ile69=
- Coding
- c.207C>T
- MANE Select
- NM_005982
- dbSNP
- rs1169502259
- Type
- single nucleotide variant
- Location
- chr14:60648983 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI 0.26 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 76.87 · 1 PDB
- Residue 69
- an α-helix
Similar variants
- SIX1 p.Arg110Gln Pathogenic/Likely pathogenic ★★ same type
- SIX1 p.Arg110Trp Pathogenic ★★ same type
- SIX1 p.Glu125Lys Pathogenic/Likely pathogenic ★★ same type
- SIX1 p.Tyr129Cys Pathogenic ★★ same type
- SIX1 p.Val106Met Likely pathogenic ★★ same type
- SIX1 p.Ala184Thr Uncertain significance ★★ same type
- SIX1 p.Arg119His Uncertain significance ★★ ⚠ same type
- SIX1 p.Arg140Gln 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-ile69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown