Is ANO7 p.Arg746Pro (c.2237G>C) pathogenic?

ANO7 p.Arg746Pro (c.2237G>C) is classified Uncertain significance in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: ambiguous (0.4253); Very rare (popmax 8.7e-05%, nfe).

How common is ANO7 p.Arg746Pro (c.2237G>C) in the general population?

ANO7 p.Arg746Pro (c.2237G>C) is very rare (popmax 8.7e-05%, nfe) (gnomAD).

What do computational predictors say about ANO7 p.Arg746Pro (c.2237G>C)?

AlphaMissense predicts ambiguous (score 0.4253) — an in-silico prediction, not a clinical call.

ANO7 p.Arg746Pro

c.2237G>C · rs201093415 · VCV2310654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.7e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4253	ambiguous
REVEL	0.341	indeterminate
SaProt	LLR -11.08	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.84	GERP -2.1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	14.01	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 R800P vs ClinVar R746P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.7e-05% European (non-Finnish) · 1/1,149,032 alleles

Overall 7.22e-05% 1/1,384,146 alleles · very rare

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.Arg746Pro
Coding: c.2237G>C
MANE Select: NM_001370694
dbSNP: rs201093415
Type: single nucleotide variant
Location: chr2:241218297 (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

HDLBP p.Gly746Glu 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-arg746pro (accessed [today's date]).

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