Is ETFB p.Val46fs (c.136del) pathogenic?

ETFB p.Val46fs (c.136del) is classified Likely pathogenic in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-21). Very rare (popmax 0.00017%, nfe); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Val46fs (c.136del)?

ETFB p.Val46fs (c.136del) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Val46fs (c.136del) in the general population?

ETFB p.Val46fs (c.136del) is very rare (popmax 0.00017%, nfe) (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.Val46fs

c.136del · rs1303961688 · VCV1805746

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

multiple acyl-CoA dehydrogenase deficiency

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 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,778 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,874 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: ETFB
Protein: p.Val46fs
Coding: c.136del
MANE Select: NM_001985
dbSNP: rs1303961688
Type: Deletion
Location: chr19:51354230 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 46: an α-helix

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.Val46= Likely benign ★ same residue
ETFB p.Arg21fs Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Pro211fs Likely pathogenic ★★ same condition
ETFB p.Glu115del Uncertain significance ★★ same condition
ETFB c.341_375+154del Likely pathogenic ★ same condition
ETFB p.Asp32fs Likely pathogenic ★ same condition
ETFB p.Gln70fs Likely pathogenic ★ same condition
ETFB p.Glu95fs 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-val46fs (accessed [today's date]).

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