ANO6 p.Ser640=
c.1920T>G · rs530970448 · VCV257144
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.193%, 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 -9.9 | GERP -4.8 |
| Overall | ||
| CADD | 0.165 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.193%
South Asian · 176/91,082 alleles
Filtering AF
0.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.161%
Overall
0.0115%
185/1,614,086 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.193% | 518 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,945 |
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.Ser640=
- Coding
- c.1920T>G
- MANE Select
- NM_001025356
- dbSNP
- rs530970448
- Type
- single nucleotide variant
- Location
- chr12:45409396 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.00
- Residue 640
- 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-ser640 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown