Is ANO3 p.Arg969Trp (c.2905C>T) pathogenic?

ANO3 p.Arg969Trp (c.2905C>T) is classified Uncertain significance in ANO3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-15). AlphaMissense: ambiguous (0.4198); Ultra-rare (popmax 0.0276%, sas); Associated with Inborn genetic diseases.

What condition is associated with ANO3 p.Arg969Trp (c.2905C>T)?

ANO3 p.Arg969Trp (c.2905C>T) is associated with Inborn genetic diseases, dystonic disorder (ClinVar).

How common is ANO3 p.Arg969Trp (c.2905C>T) in the general population?

ANO3 p.Arg969Trp (c.2905C>T) is ultra-rare (popmax 0.0276%, sas) (gnomAD).

What do computational predictors say about ANO3 p.Arg969Trp (c.2905C>T)?

AlphaMissense predicts ambiguous (score 0.4198) — an in-silico prediction, not a clinical call.

ANO3 p.Arg969Trp

c.2905C>T · rs373975805 · VCV862444

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4198	ambiguous
REVEL	0.401	indeterminate
SaProt	LLR -5.37	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.28, phastCons 0.94
Regional constraint	o/e 0.69	unconstrained · MANE · 129 kb · p 7.8e-20 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0276% South Asian · 25/90,688 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00236% 38/1,612,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0276%	3,628
Remaining individualsnot grpmax-eligible	0.00641%	15,605
African / African-American	0.00267%	37,397
European (non-Finnish)	0.000594%	168,467

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.Arg969Trp
Coding: c.2905C>T
MANE Select: NM_031418
dbSNP: rs373975805
Type: single nucleotide variant
Location: chr11:26660403 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dystonic disorder

Similar variants

ANO3 p.Arg969Gln Likely benign ★ 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 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-arg969trp (accessed [today's date]).

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