Is ANO7 p.Tyr433= (c.1299C>T) pathogenic?

ANO7 p.Tyr433= (c.1299C>T) is classified Likely benign in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Ultra-rare (popmax 0.0187%, afr).

How common is ANO7 p.Tyr433= (c.1299C>T) in the general population?

ANO7 p.Tyr433= (c.1299C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

ANO7 p.Tyr433=

c.1299C>T · rs1194319748 · VCV2652111

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP 1.1, phastCons 0.066
Overall
CADD	3.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,752 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00906%

Overall 0.00112% 18/1,603,550 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,339
Remaining individualsnot grpmax-eligible	0.00161%	61,928
European (non-Finnish)	0.000255%	391,934

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.Tyr433=
Coding: c.1299C>T
MANE Select: NM_001370694
dbSNP: rs1194319748
Type: single nucleotide variant
Location: chr2:241209575 (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.Tyr433Ser 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-tyr433 (accessed [today's date]).

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