Is ANO7 p.Pro762Arg (c.2285C>G) pathogenic?

ANO7 p.Pro762Arg (c.2285C>G) is classified Uncertain significance in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.6674); Very rare (popmax 0.00294%, eas).

How common is ANO7 p.Pro762Arg (c.2285C>G) in the general population?

ANO7 p.Pro762Arg (c.2285C>G) is very rare (popmax 0.00294%, eas) (gnomAD).

What do computational predictors say about ANO7 p.Pro762Arg (c.2285C>G)?

AlphaMissense predicts likely pathogenic (score 0.6674) — an in-silico prediction, not a clinical call.

ANO7 p.Pro762Arg

c.2285C>G · rs763317329 · VCV2229098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00294%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6674	likely pathogenic
REVEL	0.469	indeterminate
SaProt	LLR -10.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1, phastCons 0.47
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	19.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P816R vs ClinVar P762R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00294% East Asian · 1/34,018 alleles

Filtering AF 8.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.6e-05%

Overall 0.000741% 11/1,484,628 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0066%	15,149
East Asiangrpmax	0.00294%	34,018
Admixed American	0.00219%	45,738
Remaining individualsnot grpmax-eligible	0.00176%	56,924
South Asian	0.00126%	79,572
European (non-Finnish)	0.000357%	280,499

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: ANO7
Protein: p.Pro762Arg
Coding: c.2285C>G
MANE Select: NM_001370694
dbSNP: rs763317329
Type: single nucleotide variant
Location: chr2:241218345 (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 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
ANO7 c.1561+64C>T 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-pro762arg (accessed [today's date]).

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