Is ANO3 p.Pro342= (c.1026A>G) pathogenic?

ANO3 p.Pro342= (c.1026A>G) is classified Benign in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.09%, amr); Associated with dystonic disorder.

What condition is associated with ANO3 p.Pro342= (c.1026A>G)?

ANO3 p.Pro342= (c.1026A>G) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Pro342= (c.1026A>G) in the general population?

ANO3 p.Pro342= (c.1026A>G) is ultra-rare (popmax 0.09%, amr) (gnomAD).

ANO3 p.Pro342=

c.1026A>G · rs777435490 · VCV1989102

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, amr)

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 -0.83	GERP -3.5
Overall
CADD	4.683	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% Admixed American · 54/59,996 alleles

Filtering AF 0.0708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0639%

Overall 0.00347% 56/1,612,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.09%	1,111
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	8.48e-05%	1,179,014

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.Pro342=
Coding: c.1026A>G
MANE Select: NM_031418
dbSNP: rs777435490
Type: single nucleotide variant
Location: chr11:26537455 (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

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 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
ANO3 c.432+4A>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-pro342 (accessed [today's date]).

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