Is ANO6 p.Trp407fs (c.1219dup) pathogenic?

ANO6 p.Trp407fs (c.1219dup) is classified Pathogenic in ANO6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-26). Very rare (popmax 0.000339%, nfe); Associated with Scott syndrome.

What condition is associated with ANO6 p.Trp407fs (c.1219dup)?

ANO6 p.Trp407fs (c.1219dup) is associated with Scott syndrome (ClinVar).

How common is ANO6 p.Trp407fs (c.1219dup) in the general population?

ANO6 p.Trp407fs (c.1219dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Scott syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ANO6 p.Trp407fs

c.1219dup · rs2547492090 · VCV2584647

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Scott syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.16	GERP -4.8, phastCons 0.005

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,964 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,794 alleles · very rare

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: ANO6
Protein: p.Trp407fs
Coding: c.1219dup
MANE Select: NM_001025356
dbSNP: rs2547492090
Type: Duplication
Location: chr12:45388213 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.00
Residue 407: a disulfide bond

Full ANO6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Scott syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Scott syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

ANO6 p.Tyr75fs Likely pathogenic ★ same condition
ANO6 c.1387-1G>T Pathogenic ★★ same condition
ANO6 c.1308+2T>C Pathogenic ★ same condition
ANO6 p.Arg419Ter Pathogenic ★ same condition
ANO6 p.Arg638fs Likely pathogenic ★ same condition
ANO6 p.Thr506fs Likely pathogenic ★ same condition
ANO6 p.Trp358Ter Likely pathogenic ★ same condition
ANO6 c.1880+1G>A Conflicting classifications of pathogenicity ★ 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/ano6-p-trp407fs (accessed [today's date]).

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