ANO4 p.Pro864=
c.2592G>A · rs17031025 · VCV715963
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 6.23%, eas) — too common for a highly-penetrant pathogenic allele
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 -0.92 | GERP -5.8, phastCons 0.007 |
| Overall | ||
| CADD | 7.258 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.23%
East Asian · 2,795/44,864 alleles
Filtering AF
6.04%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.96%
Overall
0.187%
3,017/1,613,928 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 6.23% | 16 |
| Remaining individualsnot grpmax-eligible | 0.174% | 573 |
| South Asian | 0.0725% | 1,380 |
| Middle Eastern | 0.033% | 3,029 |
| Admixed American | 0.0133% | 7,497 |
| European (non-Finnish) | 0.00297% | 33,713 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
| African / African-American | 0.00133% | 75,002 |
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
- ANO4
- Protein
- p.Pro864=
- Coding
- c.2592G>A
- MANE Select
- NM_001286615
- dbSNP
- rs17031025
- Type
- single nucleotide variant
- Location
- chr12:101120541 (GRCh38)
- Gene constraint
- LOEUF 0.576 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.27
Similar variants
- ANO4 p.Pro864Leu Uncertain significance ★ ⚠ same residue
- ANO4 p.Phe720Leu Uncertain significance ★★ ⚠ same type
- ANO4 p.Val376Ile Likely benign ★★ same type
- ANO4 p.Asn129Lys Pathogenic ★ ⚠ same type
- ANO4 p.Asn558Lys Pathogenic ★ same type
- ANO4 p.Asn603Asp Pathogenic ★ same type
- ANO4 p.Ile562Phe Pathogenic ★ same type
- ANO4 p.Met563Lys Pathogenic ★ 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/ano4-p-pro864 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown