Is ETFB p.Ala63= (c.189C>T) pathogenic?

ETFB p.Ala63= (c.189C>T) is classified Likely benign in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). Ultra-rare (popmax 0.033%, mid); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Ala63= (c.189C>T)?

ETFB p.Ala63= (c.189C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Ala63= (c.189C>T) in the general population?

ETFB p.Ala63= (c.189C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ETFB p.Ala63=

c.189C>T · rs267605609 · VCV744045

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

multiple acyl-CoA dehydrogenase deficiency

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 -9.2	GERP -2.5
Overall
CADD	0.982	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,058 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00137% 20/1,461,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,029
South Asian	0.00659%	15,179
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.000763%	131,114

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: ETFB
Protein: p.Ala63=
Coding: c.189C>T
MANE Select: NM_001985
dbSNP: rs267605609
Type: single nucleotide variant
Location: chr19:51354177 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 63: a β-strand

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

Disease context

multiple acyl-CoA dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple acyl-CoA dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (United States)

Similar variants

ETFB c.375+1G>A Likely pathogenic ★★ same condition
ETFB c.375+1G>T Likely pathogenic ★★ same condition
ETFB p.Arg164Gln Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Arg21Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Cys42Arg Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Gln136Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Glu60Ter 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/etfb-p-ala63 (accessed [today's date]).

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