Is ANO3 p.Ser62Arg (c.186T>G) pathogenic?

ANO3 p.Ser62Arg (c.186T>G) is classified Uncertain significance in ANO3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-19). AlphaMissense: likely benign (0.1552); Ultra-rare (popmax 0.0187%, afr); Associated with dystonic disorder.

What condition is associated with ANO3 p.Ser62Arg (c.186T>G)?

ANO3 p.Ser62Arg (c.186T>G) is associated with dystonic disorder (ClinVar).

How common is ANO3 p.Ser62Arg (c.186T>G) in the general population?

ANO3 p.Ser62Arg (c.186T>G) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about ANO3 p.Ser62Arg (c.186T>G)?

AlphaMissense predicts likely benign (score 0.1552) — an in-silico prediction, not a clinical call.

ANO3 p.Ser62Arg

c.186T>G · rs138534016 · VCV2729698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.1552	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -7.77	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 0.18	GERP -2.9, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 176 kb · p 0.87 · regional, not allelic
Overall
CADD	14.72	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 0.0187% African / African-American · 14/74,880 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00093% 15/1,613,742 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,349
Admixed American	0.00167%	59,958

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.Ser62Arg
Coding: c.186T>G
MANE Select: NM_031418
dbSNP: rs138534016
Type: single nucleotide variant
Location: chr11:26442057 (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.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
ANO3 c.432+4A>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-ser62arg (accessed [today's date]).

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