Is ETFDH p.Arg342= (c.1026G>A) pathogenic?

ETFDH p.Arg342= (c.1026G>A) is classified Likely benign in ETFDH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.0117%, amr); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFDH p.Arg342= (c.1026G>A)?

ETFDH p.Arg342= (c.1026G>A) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFDH p.Arg342= (c.1026G>A) in the general population?

ETFDH p.Arg342= (c.1026G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

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

ETFDH p.Arg342=

c.1026G>A · rs994474448 · VCV2055706

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.4, phastCons 1
Overall
CADD	11.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,978 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000496% 8/1,612,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,568
European (non-Finnish)	8.48e-05%	1,178,906

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: ETFDH
Protein: p.Arg342=
Coding: c.1026G>A
MANE Select: NM_004453
dbSNP: rs994474448
Type: single nucleotide variant
Location: chr4:158699040 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.60

Full ETFDH 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

ETFDH c.1116+2T>C Likely pathogenic ★★ same condition
ETFDH c.1117-1G>A Likely pathogenic ★★ same condition
ETFDH c.1117-2A>G Pathogenic/Likely pathogenic ★★ same condition
ETFDH c.1285+1G>A Pathogenic ★★ same condition
ETFDH c.1469-1G>T Likely pathogenic ★★ same condition
ETFDH c.1690+1G>T Pathogenic ★★ same condition
ETFDH c.1690+2T>G Pathogenic/Likely pathogenic ★★ same condition
ETFDH c.1691-3C>G Pathogenic/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/etfdh-p-arg342 (accessed [today's date]).

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