ANO6 p.Phe676=
c.2028C>T · rs12308034 · VCV2065773
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.309%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.27 | acceptor loss, 16 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.26 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 10.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.309%
African / African-American · 232/75,044 alleles
Filtering AF
0.277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.264%
Overall
0.0203%
328/1,614,038 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.309% | 323 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,905 |
| Admixed American | 0.0167% | 6,000 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 0.00568% | 17,611 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
| South Asian | 0.0011% | 91,058 |
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
- ANO6
- Protein
- p.Phe676=
- Coding
- c.2028C>T
- MANE Select
- NM_001025356
- dbSNP
- rs12308034
- Type
- single nucleotide variant
- Location
- chr12:45416715 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.00
- Residue 676
- a disulfide bond
Similar variants
- ANO6 c.1387-1G>T Pathogenic ★★ same type
- ANO6 p.Arg253Cys Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg253His Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg276Gln Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg399Cys Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg635Gln Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg648Leu Uncertain significance ★★ ⚠ same type
- ANO6 p.Arg862Cys 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/ano6-p-phe676 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown