Is ETFB p.Asn188= (c.564C>T) pathogenic?

ETFB p.Asn188= (c.564C>T) is classified Likely benign in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). Ultra-rare (popmax 0.0111%, amr); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Asn188= (c.564C>T)?

ETFB p.Asn188= (c.564C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Asn188= (c.564C>T) in the general population?

ETFB p.Asn188= (c.564C>T) is ultra-rare (popmax 0.0111%, amr) (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.Asn188=

c.564C>T · rs570126169 · VCV1896177

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, amr)

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 -5	GERP -2.6
Overall
CADD	2.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% Admixed American · 6/53,848 alleles

Filtering AF 0.00479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00322%

Overall 0.00241% 38/1,575,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0111%	8,975
European (non-Finnish)	0.00241%	41,454
East Asian	0.00234%	42,690
South Asian	0.00232%	43,172
Remaining individualsnot grpmax-eligible	0.00164%	61,066

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.Asn188=
Coding: c.564C>T
MANE Select: NM_001985
dbSNP: rs570126169
Type: single nucleotide variant
Location: chr19:51346933 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 188: the 'recognition loop' region

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 p.Asn188Lys Uncertain significance ★ ⚠ same residue
ETFB p.Asn188Ser Uncertain significance ★ ⚠ same residue
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

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-asn188 (accessed [today's date]).

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