Is ETFA p.Val219fs (c.650_653dup) pathogenic?

ETFA p.Val219fs (c.650653dup) is classified Likely pathogenic in ETFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). Absent from gnomAD; Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFA p.Val219fs (c.650_653dup)?

ETFA p.Val219fs (c.650_653dup) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Val219fs (c.650_653dup) in the general population?

ETFA p.Val219fs (c.650_653dup) is absent from gnomAD (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

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

ETFA p.Val219fs

c.650_653dup · rs2543022225 · VCV2675081

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.75	GERP -3.1, phastCons 0.004

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ETFA
Protein: p.Val219fs
Coding: c.650_653dup
MANE Select: NM_000126
dbSNP: rs2543022225
Type: Duplication
Location: chr15:76285647 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 219: the 'domain ii' region; a β-strand

Full ETFA 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

ETFA p.Val219= Likely benign ★ same residue
ETFA p.Ala125fs Likely pathogenic ★★ same condition
ETFA p.Gln9fs Pathogenic/Likely pathogenic ★★ same condition
ETFA p.Gly279fs Pathogenic/Likely pathogenic ★★ same condition
ETFA p.Leu95fs Pathogenic/Likely pathogenic ★★ same condition
ETFA p.Lys232Ter Pathogenic/Likely pathogenic ★★ same condition
ETFA c.40-19dup Benign/Likely benign ★★ same condition
ETFA c.664+2dup 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/etfa-p-val219fs (accessed [today's date]).

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