Is ANO3 p.Val325fs (c.972del) pathogenic?

ANO3 p.Val325fs (c.972del) is classified Uncertain significance in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-26). Absent from gnomAD; Associated with dystonia 24.

What condition is associated with ANO3 p.Val325fs (c.972del)?

ANO3 p.Val325fs (c.972del) is associated with dystonia 24 (ClinVar).

How common is ANO3 p.Val325fs (c.972del) in the general population?

ANO3 p.Val325fs (c.972del) is absent from gnomAD (gnomAD).

ANO3 p.Val325fs

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.972del · rs1849455340 · VCV2439108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dystonia 24

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP -1.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANO3
Protein: p.Val325fs
Coding: c.972del
MANE Select: NM_031418
dbSNP: rs1849455340
Type: Deletion
Location: chr11:26534555 (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

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

ANO3 c.1290-13del Benign ★★ same condition
ANO3 c.1290-14del Benign/Likely benign ★★ same condition
ANO3 c.1290-19del Benign ★★ same condition
ANO3 c.1290-7del Benign/Likely benign ★★ same condition
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

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-val325fs (accessed [today's date]).

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