Is ACADL p.Ala368= (c.1104G>A) pathogenic?

ACADL p.Ala368= (c.1104G>A) is classified Likely benign in ACADL (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-13). Ultra-rare (popmax 0.0495%, mid); Associated with ACADL-related disorder.

What condition is associated with ACADL p.Ala368= (c.1104G>A)?

ACADL p.Ala368= (c.1104G>A) is associated with ACADL-related disorder (ClinVar).

How common is ACADL p.Ala368= (c.1104G>A) in the general population?

ACADL p.Ala368= (c.1104G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

ACADL p.Ala368=

c.1104G>A · rs140400345 · VCV3045444

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

ACADL-related disorder

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 -9	GERP -6.9
Overall
CADD	2.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,060 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00198% 32/1,613,834 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,020
African / African-American	0.0147%	6,819
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	0.00119%	84,277

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: ACADL
Protein: p.Ala368=
Coding: c.1104G>A
MANE Select: NM_001608
dbSNP: rs140400345
Type: single nucleotide variant
Location: chr2:210195219 (GRCh38)
Gene constraint: LOEUF 1.262 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.09 · 3 PDB
Residue 368: an α-helix

Full ACADL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ACADL-related disorder

Similar variants

ACADL p.Ala368Val Uncertain significance ★ ⚠ same residue
ACADL p.Ile170Val Uncertain significance ★★ ⚠ same condition
ACADL c.871-2A>G Uncertain significance ★ same condition
ACADL p.Cys166Tyr Uncertain significance ★ ⚠ same condition
ACADL p.His228Arg Uncertain significance ★ ⚠ same condition
ACADL p.Tyr282Cys Uncertain significance ⚠ same condition
ACADL c.1112+5G>A Likely benign same condition
ACADL c.1199+9A>G Likely benign 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/acadl-p-ala368 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown