ACHE p.Thr269=
c.807G>A · rs17228581 · VCV733662
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.59%, 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 -20 | |
| Overall | ||
| CADD | 0.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.59%
African / African-American · 1,193/75,060 alleles
Filtering AF
1.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.48%
Overall
0.0886%
1,426/1,610,146 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.59% | 63 |
| Admixed American | 0.115% | 869 |
| Remaining individualsnot grpmax-eligible | 0.106% | 946 |
| Middle Eastern | 0.0662% | 1,511 |
| South Asian | 0.022% | 4,550 |
| East Asian | 0.00892% | 11,210 |
| European (non-Finnish) | 0.00593% | 16,850 |
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
- ACHE
- Protein
- p.Thr269=
- Coding
- c.807G>A
- MANE Select
- NM_000665
- dbSNP
- rs17228581
- Type
- single nucleotide variant
- Location
- chr7:100893426 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 (gnomAD)
- Structure
- AlphaFold pLDDT 93.04 · 81 PDB
Similar variants
- ACHE p.Arg34Gln Benign ★★ same type
- ACHE p.Glu344= Benign/Likely benign ★★ same type
- ACHE p.Gly89Glu Benign ★★ ⚠ same type
- ACHE p.Pro135Ala Likely benign ★★ ⚠ same type
- ACHE p.Pro441= Likely benign ★★ same type
- ACHE p.Ala14Thr Uncertain significance ★ ⚠ same type
- ACHE p.Ala256Thr Uncertain significance ★ ⚠ same type
- ACHE p.Ala408Gly 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/ache-p-thr269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown