Is ANO3 p.Asp129= (c.387C>T) pathogenic?

ANO3 p.Asp129= (c.387C>T) is classified Likely benign in ANO3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-18). Ultra-rare (popmax 0.0167%, mid); Associated with dystonic disorder.

What condition is associated with ANO3 p.Asp129= (c.387C>T)?

ANO3 p.Asp129= (c.387C>T) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Asp129= (c.387C>T) in the general population?

ANO3 p.Asp129= (c.387C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

ANO3 p.Asp129=

c.387C>T · rs141892021 · VCV1086714

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Conditions

dystonic disorder

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 0.46	GERP -0.31, phastCons 1
Overall
CADD	8.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Middle Eastern · 1/5,992 alleles

Filtering AF 0.00261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00235%

Overall 0.00345% 55/1,593,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,992
Finnishnot grpmax-eligible	0.0126%	7,961
Remaining individualsnot grpmax-eligible	0.00487%	20,523
European (non-Finnish)	0.00351%	28,529
Ashkenazi Jewishnot grpmax-eligible	0.00343%	29,146
Admixed American	0.00175%	57,292

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.Asp129=
Coding: c.387C>T
MANE Select: NM_031418
dbSNP: rs141892021
Type: single nucleotide variant
Location: chr11:26463103 (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

MUC15 p.Pro129His 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
ANO3 c.2276-6T>C Uncertain significance ★★ same condition
ANO3 c.2764-5T>G 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-asp129 (accessed [today's date]).

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