Is ANO3 p.Lys139= (c.417G>A) pathogenic?

ANO3 p.Lys139= (c.417G>A) is classified Likely benign in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). Very rare (popmax 0.000175%, nfe); Associated with dystonic disorder.

What condition is associated with ANO3 p.Lys139= (c.417G>A)?

ANO3 p.Lys139= (c.417G>A) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Lys139= (c.417G>A) in the general population?

ANO3 p.Lys139= (c.417G>A) is very rare (popmax 0.000175%, nfe) (gnomAD).

ANO3 p.Lys139=

c.417G>A · rs753616592 · VCV1111668

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000175%, nfe)

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 3.2	GERP -1.9, phastCons 1
Overall
CADD	7.514	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000175% European (non-Finnish) · 2/1,143,998 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000142% 2/1,409,404 alleles · very rare

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.Lys139=
Coding: c.417G>A
MANE Select: NM_031418
dbSNP: rs753616592
Type: single nucleotide variant
Location: chr11:26463133 (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-lys139 (accessed [today's date]).

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