ACBD5 p.Glu493Lys
c.1477G>A · rs144945606 · VCV939196
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2606 | likely benign |
|---|---|---|
| REVEL | 0.1 | moderately benign-leaning |
| SaProt | LLR -8.04 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 43 kb · p 0.00076 · regional, not allelic |
| Overall | ||
| CADD | 24.2 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E502K vs ClinVar E493K) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.005% | 19,999 |
| East Asian | 0.00223% | 44,874 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
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
- ACBD5
- Protein
- p.Glu493Lys
- Coding
- c.1477G>A
- MANE Select
- NM_145698
- dbSNP
- rs144945606
- Type
- single nucleotide variant
- Location
- chr10:27204528 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 57.49 · 1 PDB
Similar variants
- ACBD5 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Arg384Trp Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Arg415Trp Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Asp429Asn Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Gln452His Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Glu312Lys Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Gly180Asp Uncertain significance ★★ ⚠ same condition
- ACBD5 p.Gly389Arg Uncertain significance ★★ ⚠ same condition
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/acbd5-p-glu493lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown