Is ETFA p.Lys232Ter (c.693dup) pathogenic?

ETFA p.Lys232Ter (c.693dup) is classified Pathogenic/Likely pathogenic in ETFA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-18). Very rare (popmax 0.00223%, eas); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFA p.Lys232Ter (c.693dup)?

ETFA p.Lys232Ter (c.693dup) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Lys232Ter (c.693dup) in the general population?

ETFA p.Lys232Ter (c.693dup) is very rare (popmax 0.00223%, eas) (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.Lys232Ter

c.693dup · rs754050501 · VCV1451237

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,812 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00112% 18/1,612,320 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,812
European (non-Finnish)	0.00144%	69,337

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: ETFA
Protein: p.Lys232Ter
Coding: c.693dup
MANE Select: NM_000126
dbSNP: rs754050501
Type: Duplication
Location: chr15:76283796 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 232: the 'domain ii' region; a modified residue (n6-acetyllysine; alternate); a modified residue (n6-succinyllysine; alternate); an α-helix

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.Lys232= 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 c.40-19dup Benign/Likely benign ★★ same condition
ETFA c.664+2dup Likely pathogenic ★ same condition
ETFA p.Ala124fs 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-lys232ter (accessed [today's date]).

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