Is ANO6 p.Arg276Ter (c.826C>T) pathogenic?

ANO6 p.Arg276Ter (c.826C>T) is classified Pathogenic in ANO6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-03-26). Very rare (popmax 0.00892%, eas); Associated with Scott syndrome.

What condition is associated with ANO6 p.Arg276Ter (c.826C>T)?

ANO6 p.Arg276Ter (c.826C>T) is associated with Scott syndrome (ClinVar).

How common is ANO6 p.Arg276Ter (c.826C>T) in the general population?

ANO6 p.Arg276Ter (c.826C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

How is Scott syndrome inherited?

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

ANO6 p.Arg276Ter

c.826C>T · rs761437689 · VCV2584644

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

Scott syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.3, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,858 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00229% 37/1,613,524 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,214
European (non-Finnish)	0.00263%	38,057
Remaining individualsnot grpmax-eligible	0.0016%	62,470
South Asian	0.0011%	91,064

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.Arg276Ter
Coding: c.826C>T
MANE Select: NM_001025356
dbSNP: rs761437689
Type: single nucleotide variant
Location: chr12:45350737 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.00

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.Arg276Gln Uncertain significance ★★ ⚠ same residue
ANO6 c.1387-1G>T Pathogenic ★★ same condition
ANO6 c.1308+2T>C Pathogenic ★ same condition
ANO6 p.Arg419Ter Pathogenic ★ same condition
ANO6 p.Trp358Ter Likely pathogenic ★ same condition
ANO6 c.1880+1G>A Conflicting classifications of pathogenicity ★ same condition
ANO6 p.Asp858= Conflicting classifications of pathogenicity ★ same condition
ANO6 c.747+1G>A Pathogenic 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-arg276ter (accessed [today's date]).

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