Is ANO6 p.Ala786= (c.2358A>G) pathogenic?

ANO6 p.Ala786= (c.2358A>G) is classified Likely benign in ANO6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-10). Very rare (popmax 0.00133%, afr).

How common is ANO6 p.Ala786= (c.2358A>G) in the general population?

ANO6 p.Ala786= (c.2358A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

ANO6 p.Ala786=

c.2358A>G · rs1315807479 · VCV3019415

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -5.4
Overall
CADD	0.537	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,946 alleles

Overall 0.000124% 2/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,946
European (non-Finnish)	8.47e-05%	1,180,013

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.Ala786=
Coding: c.2358A>G
MANE Select: NM_001025356
dbSNP: rs1315807479
Type: single nucleotide variant
Location: chr12:45421211 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.00
Residue 786: a disulfide bond

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

Similar variants

ANO6 p.Ala786Thr Uncertain significance ★ ⚠ same residue
ANO6 c.1387-1G>T Pathogenic ★★ same type
ANO6 p.Arg253Cys Uncertain significance ★★ ⚠ same type
ANO6 p.Arg253His Uncertain significance ★★ ⚠ same type
ANO6 p.Arg276Gln Uncertain significance ★★ ⚠ same type
ANO6 p.Arg399Cys Uncertain significance ★★ same type
ANO6 p.Arg635Gln Uncertain significance ★★ ⚠ same type
ANO6 p.Arg648Leu Uncertain significance ★★ ⚠ same type

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-ala786 (accessed [today's date]).

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