Is ACADM p.Asp266= (c.798C>T) pathogenic?

ACADM p.Asp266= (c.798C>T) is classified Conflicting classifications of pathogenicity in ACADM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00769%, sas); Associated with Inborn genetic diseases.

What condition is associated with ACADM p.Asp266= (c.798C>T)?

ACADM p.Asp266= (c.798C>T) is associated with Inborn genetic diseases, medium chain acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ACADM p.Asp266= (c.798C>T) in the general population?

ACADM p.Asp266= (c.798C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

ACADM p.Asp266=

c.798C>T · rs765170454 · VCV806153

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.015	GERP -3.7, phastCons 0.17
Overall
CADD	8.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,086 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00112% 18/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
Admixed American	0.005%	19,995
East Asian	0.00446%	22,437
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.000424%	235,995

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: ACADM
Protein: p.Asp266=
Coding: c.798C>T
MANE Select: NM_000016
dbSNP: rs765170454
Type: single nucleotide variant
Location: chr1:75749508 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.15 · 7 PDB
Residue 266: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: medium chain acyl-CoA dehydrogenase deficiency

Similar variants

ACADM p.Asp266Gly Pathogenic/Likely pathogenic ★★ ⚠ same residue
ACADM c.118+1G>T Likely pathogenic ★★ same condition
ACADM c.1194+1G>A Pathogenic/Likely pathogenic ★★ same condition
ACADM c.1194+2T>G Likely pathogenic ★★ same condition
ACADM c.216+1G>A Pathogenic ★★ same condition
ACADM c.216+1G>T Pathogenic/Likely pathogenic ★★ same condition
ACADM c.216+2T>C Pathogenic ★★ same condition
ACADM c.216+2T>G 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/acadm-p-asp266 (accessed [today's date]).

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