ACHE p.Pro441=
c.1323C>T · rs550436794 · VCV718317
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
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 -6.2 | |
| Overall | ||
| CADD | 4.549 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,058 alleles
Filtering AF
0.043%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.00998%
161/1,612,772 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| South Asian | 0.0308% | 3,251 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,938 |
| European (non-Finnish) | 0.00967% | 10,346 |
| East Asian | 0.00669% | 14,947 |
| African / African-American | 0.00133% | 74,920 |
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.Pro441=
- Coding
- c.1323C>T
- MANE Select
- NM_000665
- dbSNP
- rs550436794
- Type
- single nucleotide variant
- Location
- chr7:100892564 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 (gnomAD)
- Structure
- AlphaFold pLDDT 93.04 · 81 PDB
- Residue 441
- a disulfide bond; an α-helix
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.Thr269= Benign/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-pro441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown