Is ANO3 p.Ser55Phe (c.164C>T) pathogenic?

ANO3 p.Ser55Phe (c.164C>T) is classified Conflicting classifications of pathogenicity in ANO3 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-05-01). AlphaMissense: likely benign (0.112); Rare (popmax 0.883%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ANO3 p.Ser55Phe (c.164C>T)?

ANO3 p.Ser55Phe (c.164C>T) is associated with Inborn genetic diseases, dystonic disorder, dystonia 24 (ClinVar).

How common is ANO3 p.Ser55Phe (c.164C>T) in the general population?

ANO3 p.Ser55Phe (c.164C>T) is rare (popmax 0.883%, nfe) (gnomAD).

What do computational predictors say about ANO3 p.Ser55Phe (c.164C>T)?

AlphaMissense predicts likely benign (score 0.112) — an in-silico prediction, not a clinical call.

ANO3 p.Ser55Phe

c.164C>T · rs61746297 · VCV412872

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.112 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.883%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.112	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.08	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 7.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 176 kb · p 0.87 · regional, not allelic
Overall
CADD	25.8	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 0.883% European (non-Finnish) · 10,424/1,180,008 alleles

Filtering AF 0.869% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.863%

Overall 0.731% 11,796/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.883%	113
Finnishnot grpmax-eligible	0.703%	142
Middle Eastern	0.594%	168
Remaining individualsnot grpmax-eligible	0.547%	183
South Asian	0.351%	285
Admixed American	0.22%	455
African / African-American	0.116%	863
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
East Asian	0.00223%	44,878

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.Ser55Phe
Coding: c.164C>T
MANE Select: NM_031418
dbSNP: rs61746297
Type: single nucleotide variant
Location: chr11:26442035 (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 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-ser55phe (accessed [today's date]).

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