ANO6 p.Ser747=
c.2241G>A · rs775982074 · VCV2717136
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0423%, 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 0.16 | GERP -5.4, phastCons 0.25 |
| Overall | ||
| CADD | 10.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0423%
East Asian · 19/44,902 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.023%
Overall
0.00341%
55/1,614,010 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0423% | 2,363 |
| Admixed American | 0.0133% | 7,499 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| South Asian | 0.00439% | 22,770 |
| African / African-American | 0.004% | 24,975 |
| European (non-Finnish) | 0.00153% | 65,557 |
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.Ser747=
- Coding
- c.2241G>A
- MANE Select
- NM_001025356
- dbSNP
- rs775982074
- Type
- single nucleotide variant
- Location
- chr12:45421094 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.00
Similar variants
- ANO6 p.Ser747Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser747 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown