Is ANO7 p.Arg489Cys (c.1465C>T) pathogenic?

ANO7 p.Arg489Cys (c.1465C>T) is classified Uncertain significance in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.2457); Ultra-rare (popmax 0.0646%, eas).

How common is ANO7 p.Arg489Cys (c.1465C>T) in the general population?

ANO7 p.Arg489Cys (c.1465C>T) is ultra-rare (popmax 0.0646%, eas) (gnomAD).

What do computational predictors say about ANO7 p.Arg489Cys (c.1465C>T)?

AlphaMissense predicts likely benign (score 0.2457) — an in-silico prediction, not a clinical call.

ANO7 p.Arg489Cys

c.1465C>T · rs184837414 · VCV3127129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0646%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2457	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -11.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.79	GERP -1.9
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	20.2	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 R543C vs ClinVar R489C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0646% East Asian · 29/44,884 alleles

Filtering AF 0.0461% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0399%

Overall 0.00613% 99/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0646%	1,548
Remaining individualsnot grpmax-eligible	0.008%	12,499
Admixed American	0.00666%	15,008
European (non-Finnish)	0.00492%	20,345
South Asian	0.0022%	45,537
African / African-American	0.00133%	75,072

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: ANO7
Protein: p.Arg489Cys
Coding: c.1465C>T
MANE Select: NM_001370694
dbSNP: rs184837414
Type: single nucleotide variant
Location: chr2:241210474 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.56

Full ANO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO7 p.Arg489Gly Uncertain significance ★ ⚠ same residue
ANO7 c.1077+10G>A Benign ★★ same type
ANO7 c.1077+73C>A Benign ★★ same type
ANO7 c.108+183T>G Benign ★★ same type
ANO7 c.1359+129A>G Benign ★★ same type
ANO7 c.1359+23G>A Benign ★★ same type
ANO7 c.1459-5G>A Benign ★★ same type
ANO7 c.1561+106T>C 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/ano7-p-arg489cys (accessed [today's date]).

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