Is ACADS p.Ala276fs (c.826del) pathogenic?

ACADS p.Ala276fs (c.826del) is classified Pathogenic in ACADS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). Very rare (popmax 0.00267%, afr); Associated with ACADS-related disorder.

What condition is associated with ACADS p.Ala276fs (c.826del)?

ACADS p.Ala276fs (c.826del) is associated with ACADS-related disorder (ClinVar).

How common is ACADS p.Ala276fs (c.826del) in the general population?

ACADS p.Ala276fs (c.826del) is very rare (popmax 0.00267%, afr) (gnomAD).

ACADS p.Ala276fs

c.826del · rs1318266542 · VCV2631279

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

ACADS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.1	GERP -4
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,954 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,254 alleles · very rare

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: ACADS
Protein: p.Ala276fs
Coding: c.826del
MANE Select: NM_000017
dbSNP: rs1318266542
Type: Deletion
Location: chr12:120738563 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.58 · 4 PDB
Residue 276: an α-helix

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

Disease context

ACADS-related disorder

Similar variants

ACADS p.Ala276Thr Uncertain significance ★★ ⚠ same residue
ACADS p.Leu65fs Likely pathogenic ★ same condition
ACADS p.Ala276Ser Uncertain significance ★ ⚠ same residue
ACADS p.Ala199Val Likely pathogenic ★★ same condition
ACADS p.Arg107Cys Pathogenic ★★ same condition
ACADS p.Arg380Trp Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg383Cys Pathogenic/Likely pathogenic ★★ same condition
ACADS p.Arg46Trp Pathogenic/Likely pathogenic ★★ 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/acads-p-ala276fs (accessed [today's date]).

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