Is ANO3 p.Ser116= (c.348A>G) pathogenic?

ANO3 p.Ser116= (c.348A>G) is classified Benign/Likely benign in ANO3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-28). Rare (popmax 0.218%, afr); Associated with dystonia 24.

What condition is associated with ANO3 p.Ser116= (c.348A>G)?

ANO3 p.Ser116= (c.348A>G) is associated with dystonia 24, dystonic disorder (ClinVar).

How common is ANO3 p.Ser116= (c.348A>G) in the general population?

ANO3 p.Ser116= (c.348A>G) is rare (popmax 0.218%, afr) (gnomAD).

ANO3 p.Ser116=

Q: How is Cranio-cervical dystonia with laryngeal and upper-limb involvement inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.348A>G · rs138889073 · VCV526221

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.218%, afr)

Conditions

dystonia 24

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 2.5	GERP -0.72, phastCons 1
Overall
CADD	10.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.218% African / African-American · 162/74,196 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.0189% 301/1,595,220 alleles · rare exomes 187/1,443,274 · genomes 114/151,946 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.218%	458
Admixed American	0.061%	1,639
Middle Eastern	0.0501%	1,998
Remaining individualsnot grpmax-eligible	0.0357%	2,801
European (non-Finnish)	0.00675%	14,817

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.Ser116=
Coding: c.348A>G
MANE Select: NM_031418
dbSNP: rs138889073
Type: single nucleotide variant
Location: chr11:26463064 (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

dystonia 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dystonic disorder

For Cranio-cervical dystonia with laryngeal and upper-limb involvement (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

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-ser116 (accessed [today's date]).

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