Is ETFA p.Phe2= (c.6C>T) pathogenic?

ETFA p.Phe2= (c.6C>T) is classified Conflicting classifications of pathogenicity in ETFA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Rare (popmax 0.261%, afr); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFA p.Phe2= (c.6C>T)?

ETFA p.Phe2= (c.6C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Phe2= (c.6C>T) in the general population?

ETFA p.Phe2= (c.6C>T) is rare (popmax 0.261%, afr) (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.Phe2=

c.6C>T · rs749929239 · VCV284234

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.261%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -1.6, phastCons 0.009
Overall
CADD	7.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.261% African / African-American · 193/74,016 alleles

Filtering AF 0.231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.219%

Overall 0.0134% 210/1,564,000 alleles · rare exomes 102/1,411,622 · genomes 108/152,378 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.261%	384
Remaining individualsnot grpmax-eligible	0.0115%	8,658
East Asian	0.00236%	42,336
Admixed American	0.00189%	52,972
European (non-Finnish)	0.000692%	144,405

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.Phe2=
Coding: c.6C>T
MANE Select: NM_000126
dbSNP: rs749929239
Type: single nucleotide variant
Location: chr15:76311383 (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 c.186+1G>A Likely pathogenic ★★ same condition
ETFA c.39+1G>A Likely pathogenic ★★ same condition
ETFA c.451+1G>A Likely pathogenic ★★ same condition
ETFA c.452-2A>G Likely pathogenic ★★ same condition
ETFA c.664+1G>A Likely pathogenic ★★ same condition
ETFA c.665-1G>A Likely pathogenic ★★ same condition
ETFA p.Arg122Lys Likely pathogenic ★★ same condition
ETFA p.Arg18Ter 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/etfa-p-phe2 (accessed [today's date]).

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