Is ANO3 p.Asp238= (c.714C>T) pathogenic?

ANO3 p.Asp238= (c.714C>T) is classified Benign/Likely benign in ANO3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-29). Rare (popmax 0.864%, afr); Associated with dystonic disorder.

What condition is associated with ANO3 p.Asp238= (c.714C>T)?

ANO3 p.Asp238= (c.714C>T) is associated with dystonic disorder, dystonia 24 (ClinVar).

How common is ANO3 p.Asp238= (c.714C>T) in the general population?

ANO3 p.Asp238= (c.714C>T) is rare (popmax 0.864%, afr) (gnomAD).

ANO3 p.Asp238=

c.714C>T · rs146532706 · VCV412870

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.864%, afr)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss, 23 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.72	GERP -3
Overall
CADD	8.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.864% African / African-American · 645/74,664 alleles

Filtering AF 0.809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.787%

Overall 0.049% 788/1,609,678 alleles · rare exomes 380/1,457,828 · genomes 408/151,850 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.864%	116
Remaining individualsnot grpmax-eligible	0.0674%	1,484
Admixed American	0.064%	1,563
Middle Eastern	0.0165%	6,050
Finnishnot grpmax-eligible	0.00939%	10,646
South Asian	0.00443%	22,554
European (non-Finnish)	0.00441%	22,656

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.Asp238=
Coding: c.714C>T
MANE Select: NM_031418
dbSNP: rs146532706
Type: single nucleotide variant
Location: chr11:26525656 (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

Also linked: dystonia 24

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 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-asp238 (accessed [today's date]).

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