Is ETFA p.Ter334MetextTer? (c.999dup) pathogenic?

ETFA p.Ter334MetextTer? (c.999dup) is classified Uncertain significance in ETFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). Very rare (popmax 0.000174%, nfe); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFA p.Ter334MetextTer? (c.999dup)?

ETFA p.Ter334MetextTer? (c.999dup) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Ter334MetextTer? (c.999dup) in the general population?

ETFA p.Ter334MetextTer? (c.999dup) is very rare (popmax 0.000174%, nfe) (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.Ter334MetextTer?

c.999dup · VCV4855833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, 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	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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 0.000174% European (non-Finnish) · 2/1,147,034 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000127% 2/1,577,586 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: ETFA
Protein: p.Ter334MetextTer?
Coding: c.999dup
MANE Select: NM_000126
Type: Duplication
Location: chr15:76216561 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB

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.Ter334Leu Uncertain significance ★ 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-ter334metextter (accessed [today's date]).

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