ACHE p.His478=
c.1434C>T · rs151107784 · VCV737321
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -5.3 |
| Overall | ||
| CADD | 6.313 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
African / African-American · 16/72,836 alleles
Filtering AF
0.0138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.00694%
108/1,555,828 alleles · ultra-rare
exomes 91/1,405,090 · genomes 17/150,738 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.022% | 4,552 |
| Middle Eastern | 0.0173% | 5,796 |
| European (non-Finnish) | 0.00742% | 13,473 |
| Admixed American | 0.0037% | 26,999 |
| Remaining individualsnot grpmax-eligible | 0.00335% | 29,890 |
| South Asian | 0.00236% | 42,300 |
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.His478=
- Coding
- c.1434C>T
- MANE Select
- NM_000665
- dbSNP
- rs151107784
- Type
- single nucleotide variant
- Location
- chr7:100892453 (GRCh38)
- Gene constraint
- LOEUF 0.546 · pLI 0.81 (gnomAD)
- Structure
- AlphaFold pLDDT 93.04 · 81 PDB
- Residue 478
- a binding site; an active site; a turn
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.Thr269= Benign/Likely benign ★★ same type
- ACHE p.Ala14Thr Uncertain significance ★ ⚠ same type
- ACHE p.Ala256Thr 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-his478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown