SIX3 p.Glu285=
c.855G>A · rs758933447 · VCV747731
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00698%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.4 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 11.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00698%
East Asian · 3/43,008 alleles
Filtering AF
0.00185%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00105%
Overall
0.000508%
8/1,574,474 alleles · very rare
exomes 6/1,422,252 · genomes 2/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00698% | 14,336 |
| African / African-American | 0.0054% | 18,515 |
| European (non-Finnish) | 8.57e-05% | 1,167,290 |
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
- SIX3
- Protein
- p.Glu285=
- Coding
- c.855G>A
- MANE Select
- NM_005413
- dbSNP
- rs758933447
- Type
- single nucleotide variant
- Location
- chr2:44944616 (GRCh38)
- Gene constraint
- LOEUF 0.387 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 70.38
- Residue 285
- the 'disordered' 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-glu285 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown