Is ACAD8 p.Arg206Ter (c.616C>T) pathogenic?

ACAD8 p.Arg206Ter (c.616C>T) is classified Pathogenic in ACAD8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-19). Very rare (popmax 0.00935%, afr); Associated with Inborn genetic diseases.

What condition is associated with ACAD8 p.Arg206Ter (c.616C>T)?

ACAD8 p.Arg206Ter (c.616C>T) is associated with Inborn genetic diseases, isobutyryl-CoA dehydrogenase deficiency (ClinVar).

How common is ACAD8 p.Arg206Ter (c.616C>T) in the general population?

ACAD8 p.Arg206Ter (c.616C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

ACAD8 p.Arg206Ter

c.616C>T · rs369445365 · VCV2074051

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.34	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
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 0.00935% African / African-American · 7/74,896 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00124% 20/1,613,996 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,699
Admixed American	0.00333%	29,991
South Asian	0.0022%	45,540
European (non-Finnish)	0.000763%	131,115

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: ACAD8
Protein: p.Arg206Ter
Coding: c.616C>T
MANE Select: NM_014384
dbSNP: rs369445365
Type: single nucleotide variant
Location: chr11:134259656 (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 206: a β-strand

Full ACAD8 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: isobutyryl-CoA dehydrogenase deficiency

Similar variants

ACAD8 p.Arg206Gln Uncertain significance ★ ⚠ same residue
ACAD8 p.Arg206Gly Uncertain significance ★ ⚠ same residue
ACAD8 p.Arg296Ter Pathogenic ★★ same condition
ACAD8 p.Gly377Ser Pathogenic/Likely pathogenic ★★ same condition
ACAD8 p.Gly96Ser Pathogenic ★★ ⚠ same condition
ACAD8 p.Met128Ile Pathogenic/Likely pathogenic ★★ same condition
ACAD8 p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
ACAD8 c.841+6A>C 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-arg206ter (accessed [today's date]).

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