Is ANO3 p.Ala41Val (c.122C>T) pathogenic?

ANO3 p.Ala41Val (c.122C>T) is classified Uncertain significance in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). AlphaMissense: likely benign (0.158); Rare (popmax 0.35%, eas); Associated with dystonic disorder.

What condition is associated with ANO3 p.Ala41Val (c.122C>T)?

ANO3 p.Ala41Val (c.122C>T) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Ala41Val (c.122C>T) in the general population?

ANO3 p.Ala41Val (c.122C>T) is rare (popmax 0.35%, eas) (gnomAD).

What do computational predictors say about ANO3 p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.158) — an in-silico prediction, not a clinical call.

ANO3 p.Ala41Val

c.122C>T · rs759292156 · VCV579456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.158 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.35%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.158	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -0.023, phastCons 0.003
Regional constraint	o/e 1.01	unconstrained · MANE · 176 kb · p 0.87 · regional, not allelic
Overall
CADD	13.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.35% East Asian · 157/44,884 alleles

Filtering AF 0.305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.288%

Overall 0.00998% 161/1,613,964 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.35%	286
Remaining individualsnot grpmax-eligible	0.0064%	15,622

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.Ala41Val
Coding: c.122C>T
MANE Select: NM_031418
dbSNP: rs759292156
Type: single nucleotide variant
Location: chr11:26441993 (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.Ala41Ser Uncertain significance ★★ ⚠ same residue
ANO3 p.Ala41Thr Uncertain significance ★★ ⚠ same residue
ANO3 p.Ala41Pro Uncertain significance ★ ⚠ same residue
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

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-ala41val (accessed [today's date]).

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