Is ANO2 p.Ile547Val (c.1639A>G) pathogenic?

ANO2 p.Ile547Val (c.1639A>G) is classified Benign in ANO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-02). AlphaMissense: likely benign (0.0661); Rare (popmax 0.768%, nfe).

How common is ANO2 p.Ile547Val (c.1639A>G) in the general population?

ANO2 p.Ile547Val (c.1639A>G) is rare (popmax 0.768%, nfe) (gnomAD).

What do computational predictors say about ANO2 p.Ile547Val (c.1639A>G)?

AlphaMissense predicts likely benign (score 0.0661) — an in-silico prediction, not a clinical call.

ANO2 p.Ile547Val

c.1639A>G · rs200078432 · VCV770983

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0661 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.768%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0661	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.04	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 5	GERP 0.59, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 382 kb · p 0.6 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I552V vs ClinVar I547V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.768% European (non-Finnish) · 8,960/1,167,410 alleles

Filtering AF 0.754% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.749%

Overall 0.689% 10,883/1,580,150 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.31%	43
European (non-Finnish)grpmax	0.768%	130
Remaining individualsnot grpmax-eligible	0.543%	184
Ashkenazi Jewishnot grpmax-eligible	0.119%	838
African / African-American	0.102%	980
Admixed American	0.0541%	1,849
South Asian	0.00118%	84,644

Finnish 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: ANO2
Protein: p.Ile547Val
Coding: c.1639A>G
MANE Select: NM_001364791
dbSNP: rs200078432
Type: single nucleotide variant
Location: chr12:5635329 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.81

Full ANO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO2 c.1435-244C>T Benign ★★ ⚠ same type
ANO2 c.785+6T>A Likely benign ★ same type
ANO2 p.Arg89His Likely benign ★ same type
ANO2 p.Gly966= Likely benign ★ same type
ANO2 p.Pro825Leu Likely benign ★ 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/ano2-p-ile547val (accessed [today's date]).

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