ACAD8 p.Phe136Leu
c.406T>C · VCV4208819
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9712 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9712 | likely pathogenic · top 7% in ACAD8 |
|---|---|---|
| REVEL | 0.923 | moderately pathogenic-leaning |
| SaProt | LLR -9.03 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 11 kb · p 0.076 · regional, not allelic |
| Overall | ||
| CADD | 26.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACAD8
- Protein
- p.Phe136Leu
- Coding
- c.406T>C
- MANE Select
- NM_014384
- Type
- single nucleotide variant
- Location
- chr11:134258540 (GRCh38)
- Gene constraint
- LOEUF 1.11 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 94.19 · 1 PDB
- Residue 136
- an α-helix
Similar variants
- ACAD8 p.Phe136= Benign/Likely benign ★★ same residue
- ACAD8 p.Arg206Ter Pathogenic ★★ same condition
- ACAD8 c.841+6A>C Uncertain significance ★★ same condition
- ACAD8 p.Ala113Thr Uncertain significance ★★ ⚠ same condition
- ACAD8 p.Arg102His Uncertain significance ★★ ⚠ same condition
- ACAD8 p.Arg244Gly Uncertain significance ★★ ⚠ same condition
- ACAD8 p.Asp346Asn Uncertain significance ★★ ⚠ same condition
- ACAD8 p.Glu44Lys 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/acad8-p-phe136leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown