Is ANO7 p.Arg442His (c.1325G>A) pathogenic?

ANO7 p.Arg442His (c.1325G>A) is classified Uncertain significance in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.2538); Ultra-rare (popmax 0.0549%, afr).

How common is ANO7 p.Arg442His (c.1325G>A) in the general population?

ANO7 p.Arg442His (c.1325G>A) is ultra-rare (popmax 0.0549%, afr) (gnomAD).

What do computational predictors say about ANO7 p.Arg442His (c.1325G>A)?

AlphaMissense predicts likely benign (score 0.2538) — an in-silico prediction, not a clinical call.

ANO7 p.Arg442His

c.1325G>A · rs201707610 · VCV2341786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2538 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2538	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.3, phastCons 0.051
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	18.96	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 R496H vs ClinVar R442H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0549% African / African-American · 41/74,672 alleles

Filtering AF 0.0415% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0369%

Overall 0.0114% 182/1,593,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0549%	1,821
Middle Eastern	0.046%	2,174
East Asian	0.0201%	4,970
Remaining individualsnot grpmax-eligible	0.0162%	6,157
South Asian	0.0147%	6,819
Admixed American	0.0103%	9,741
European (non-Finnish)	0.00854%	11,705
Finnishnot grpmax-eligible	0.00163%	61,460

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.Arg442His
Coding: c.1325G>A
MANE Select: NM_001370694
dbSNP: rs201707610
Type: single nucleotide variant
Location: chr2:241209601 (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.Arg442Cys Uncertain significance ★ ⚠ same residue
ANO7 p.Arg442Leu 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

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-arg442his (accessed [today's date]).

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