Is ANO3 p.Val697Asp (c.2090T>A) pathogenic?

ANO3 p.Val697Asp (c.2090T>A) is classified Uncertain significance in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). AlphaMissense: likely pathogenic (0.9771); Absent from gnomAD v4.1; Associated with dystonia 24.

What condition is associated with ANO3 p.Val697Asp (c.2090T>A)?

ANO3 p.Val697Asp (c.2090T>A) is associated with dystonia 24 (ClinVar).

How common is ANO3 p.Val697Asp (c.2090T>A) in the general population?

ANO3 p.Val697Asp (c.2090T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANO3 p.Val697Asp (c.2090T>A)?

AlphaMissense predicts likely pathogenic (score 0.9771) — an in-silico prediction, not a clinical call.

ANO3 p.Val697Asp

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.2090T>A · rs2538999445 · VCV3251964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonia 24

Computational evidence

Protein change
AlphaMissense	0.9771	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 129 kb · p 7.8e-20 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANO3
Protein: p.Val697Asp
Coding: c.2090T>A
MANE Select: NM_031418
dbSNP: rs2538999445
Type: single nucleotide variant
Location: chr11:26639190 (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 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 p.Asn603Asp Uncertain significance ★★ ⚠ same condition
ANO3 p.Gln248Pro Uncertain significance ★★ ⚠ same condition
ANO3 p.Ile767Met 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-val697asp (accessed [today's date]).

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