Is ANO6 p.Glu16Asp (c.48G>C) pathogenic?

ANO6 p.Glu16Asp (c.48G>C) is classified Conflicting classifications of pathogenicity in ANO6 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0597); Very rare (popmax 0.0044%, sas); Associated with Inborn genetic diseases.

What condition is associated with ANO6 p.Glu16Asp (c.48G>C)?

ANO6 p.Glu16Asp (c.48G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ANO6 p.Glu16Asp (c.48G>C) in the general population?

ANO6 p.Glu16Asp (c.48G>C) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about ANO6 p.Glu16Asp (c.48G>C)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

ANO6 p.Glu16Asp

c.48G>C · rs140379296 · VCV3127117

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.17	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 -12	GERP -2
Regional constraint	o/e 0.85	unconstrained · MANE · 213 kb · p 7e-07 · regional, not allelic
Overall
CADD	5.915	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 0.0044% South Asian · 4/90,868 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.00391% 63/1,612,728 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.112%	896
Remaining individualsnot grpmax-eligible	0.00481%	20,808
South Asiangrpmax	0.0044%	22,717
Admixed American	0.00334%	29,960
Finnishnot grpmax-eligible	0.00314%	31,896
East Asian	0.00223%	44,826
European (non-Finnish)	0.00153%	65,524

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu16Asp
Coding: c.48G>C
MANE Select: NM_001025356
dbSNP: rs140379296
Type: single nucleotide variant
Location: chr12:45216369 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANO6 p.Arg253Cys Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg253His Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg276Gln Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg399Cys Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg635Gln Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg648Leu Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg862Cys Uncertain significance ★★ ⚠ same condition
ANO6 p.Arg896Gln 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/ano6-p-glu16asp (accessed [today's date]).

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