Is ANO3 p.Pro894= (c.2682C>T) pathogenic?

ANO3 p.Pro894= (c.2682C>T) is classified Benign in ANO3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 75%, sas) — too common for a highly-penetrant pathogenic allele; Associated with dystonic disorder.

What condition is associated with ANO3 p.Pro894= (c.2682C>T)?

ANO3 p.Pro894= (c.2682C>T) is associated with dystonic disorder, dystonia 24 (ClinVar).

ANO3 p.Pro894=

Q: How common is ANO3 p.Pro894= (c.2682C>T) in the general population?

ANO3 p.Pro894= (c.2682C>T) is common (popmax 75%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2682C>T · rs10835051 · VCV1167539

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 75%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

dystonic disorder

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 -1.9	GERP -3.7
Overall
CADD	3.872	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75% South Asian · 68,128/90,864 alleles

Filtering AF 74.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 74.3%

Overall 63.9% 1,025,676/1,605,074 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	75%	1
Ashkenazi Jewishnot grpmax-eligible	74.7%	1
Finnishnot grpmax-eligible	66.6%	2
Middle Eastern	65.8%	2
European (non-Finnish)	65.4%	2
Remaining individualsnot grpmax-eligible	62.9%	2
Admixed American	54.1%	2
Amishnot grpmax-eligible	54%	2
East Asian	53.1%	2
African / African-American	34.8%	3

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.Pro894=
Coding: c.2682C>T
MANE Select: NM_031418
dbSNP: rs10835051
Type: single nucleotide variant
Location: chr11:26656400 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.30

Full ANO3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dystonia 24

Similar variants

ANO3 p.Ala657Thr Likely pathogenic ★★ same condition
ANO3 p.Asn648Ser Pathogenic/Likely pathogenic ★★ same condition
ANO3 p.Glu510Lys Pathogenic/Likely pathogenic ★★ same condition
ANO3 p.Gly567Arg Likely pathogenic ★★ ⚠ same condition
ANO3 p.Ile607Phe 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

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-pro894 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown