SIX2 p.Ala15=
c.45G>T · rs201430813 · VCV2885927
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.137%, afr)
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 -0.72 | GERP -1.6, phastCons 0.008 |
| Overall | ||
| CADD | 12.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.137%
African / African-American · 103/74,936 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.0083%
133/1,601,762 alleles · rare
exomes 65/1,449,470 · genomes 68/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.137% | 728 |
| Remaining individualsnot grpmax-eligible | 0.0225% | 4,439 |
| Middle Eastern | 0.0207% | 4,822 |
| Admixed American | 0.0185% | 5,409 |
| South Asian | 0.00331% | 30,179 |
| European (non-Finnish) | 8.49e-05% | 1,177,902 |
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
- SIX2
- Protein
- p.Ala15=
- Coding
- c.45G>T
- MANE Select
- NM_016932
- dbSNP
- rs201430813
- Type
- single nucleotide variant
- Location
- chr2:45009066 (GRCh38)
- Gene constraint
- LOEUF 1.24 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.99
Similar variants
- SIX2 p.Asn280Ser Uncertain significance ★★ ⚠ same type
- SIX2 p.Gly220Val Uncertain significance ★★ ⚠ same type
- SIX2 p.Gly261Ser Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro235Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro236Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro250Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Pro258Leu Uncertain significance ★★ ⚠ same type
- SIX2 p.Ser212Trp 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/six2-p-ala15 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown