ANO8 p.Val758=
c.2274T>C · VCV4941439
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 86.1%, afr) — 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 -7.1 | GERP -4.1 |
| Overall | ||
| CADD | 0.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
86.1%
African / African-American · 64,642/75,052 alleles
Filtering AF
85.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 85.3%
Overall
70.2%
1,132,694/1,614,094 alleles · common
exomes 1,022,061/1,461,820 · genomes 110,633/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 86.1% | 1 |
| Finnishnot grpmax-eligible | 81.1% | 1 |
| European (non-Finnish) | 72.1% | 1 |
| Remaining individualsnot grpmax-eligible | 69.1% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 66.3% | 2 |
| South Asian | 62.7% | 2 |
| Middle Eastern | 61.7% | 2 |
| Amishnot grpmax-eligible | 56.4% | 2 |
| Admixed American | 51% | 2 |
| East Asian | 23.9% | 4 |
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
- ANO8
- Protein
- p.Val758=
- Coding
- c.2274T>C
- MANE Select
- NM_020959
- Type
- single nucleotide variant
- Location
- chr19:17327833 (GRCh38)
- Gene constraint
- LOEUF 0.795 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.82
Similar variants
- ANO8 p.Ala1004Asp Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1048Pro Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1119Thr Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1119Val Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1167Thr Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1170Asp Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1170Thr Uncertain significance ★ ⚠ same type
- ANO8 p.Ala1184Thr Uncertain significance ★ ⚠ 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/ano8-p-val758 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown