ANO3 p.Thr216=
c.648G>A · rs769596059 · VCV1091334
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00492%, nfe)
Conditions
1
dystonic disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.8 |
| Overall | ||
| CADD | 0.999 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00492%
European (non-Finnish) · 58/1,178,266 alleles
Filtering AF
0.00386%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00353%
Overall
0.00379%
61/1,611,486 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00492% | 20,315 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,182 |
| Admixed American | 0.00167% | 59,920 |
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.Thr216=
- Coding
- c.648G>A
- MANE Select
- NM_031418
- dbSNP
- rs769596059
- Type
- single nucleotide variant
- Location
- chr11:26516883 (GRCh38)
- Gene constraint
- LOEUF 0.911 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.30
Similar variants
- ANO3 p.Thr216Met 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-thr216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown