ANO6 p.Leu550=
c.1650C>G · rs200199011 · VCV2056697
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0637%, sas)
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 -1.6 | GERP -5.4 |
| Overall | ||
| CADD | 0.302 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0637%
South Asian · 58/91,084 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0458%
Overall
0.0242%
391/1,613,928 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0637% | 1,570 |
| Admixed American | 0.0383% | 2,609 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,716 |
| Middle Eastern | 0.0329% | 3,040 |
| European (non-Finnish) | 0.0236% | 4,244 |
| African / African-American | 0.00534% | 18,731 |
| Finnishnot grpmax-eligible | 0.00312% | 32,011 |
| East Asian | 0.00223% | 44,858 |
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.Leu550=
- Coding
- c.1650C>G
- MANE Select
- NM_001025356
- dbSNP
- rs200199011
- Type
- single nucleotide variant
- Location
- chr12:45403109 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.00
- Residue 550
- 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-leu550 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown