Is ETFB c.216+18del pathogenic?

ETFB c.216+18del is classified Benign in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-18). Very rare (popmax 0.00537%, afr); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB c.216+18del?

ETFB c.216+18del is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB c.216+18del in the general population?

ETFB c.216+18del is very rare (popmax 0.00537%, afr) (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

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

ETFB c.216+18del

rs1986010144 · VCV2117895

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00537%, afr)

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +18	near-intronic (+18 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8	GERP -0.67
Non-coding constraint	Z 2.40	1 kb window · o/e 0.84 · regional · uncalibrated
Overall
CADD	0.915	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	MSR1 satellite · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00537% African / African-American · 4/74,422 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000274% 4/1,460,120 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
Coding: c.216+18del
MANE Select: NM_001985
dbSNP: rs1986010144
Type: Deletion
Location: chr19:51354132 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB

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.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
ETFB p.Gly123fs 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-c-216-plus-18del (accessed [today's date]).

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