ANO3 p.Tyr419=
c.1257T>C · rs768657100 · VCV2843149
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
Conditions
1
dystonic disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.59 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -0.6 |
| Overall | ||
| CADD | 5.638 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,046 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.0018%
29/1,611,984 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,503 |
| Admixed American | 0.00835% | 11,971 |
| European (non-Finnish) | 0.000849% | 117,850 |
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
- ANO3
- Protein
- p.Tyr419=
- Coding
- c.1257T>C
- MANE Select
- NM_031418
- dbSNP
- rs768657100
- Type
- single nucleotide variant
- Location
- chr11:26547518 (GRCh38)
- Gene constraint
- LOEUF 0.911 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.30
Similar variants
- ANO3 p.Tyr419Cys Uncertain significance ★★ ⚠ same residue
- ANO3 p.Ala657Thr Likely pathogenic ★★ same condition
- ANO3 p.Asn648Ser Pathogenic/Likely pathogenic ★★ same condition
- ANO3 p.Glu510Lys Pathogenic/Likely pathogenic ★★ same condition
- ANO3 c.1836+4A>C Uncertain significance ★★ same condition
- ANO3 c.2141+1G>A Uncertain significance ★★ same condition
- ANO3 c.2276-6T>C Uncertain significance ★★ same condition
- ANO3 c.2764-5T>G Uncertain significance ★★ same condition
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/ano3-p-tyr419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown