ANO6 p.Cys806=
c.2418C>T · rs374562590 · VCV1988892
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00644%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.49 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.38 | loss · gain 0.35 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 2.6, phastCons 1 |
| Overall | ||
| CADD | 21.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00644%
European (non-Finnish) · 76/1,179,850 alleles
Filtering AF
0.00528%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.00521%
84/1,613,786 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00644% | 15,524 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,619 |
| Admixed American | 0.00333% | 29,988 |
| African / African-American | 0.00267% | 37,464 |
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.Cys806=
- Coding
- c.2418C>T
- MANE Select
- NM_001025356
- dbSNP
- rs374562590
- Type
- single nucleotide variant
- Location
- chr12:45421271 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.00
- Residue 806
- 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-cys806 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown