Is ETFA p.Thr327= (c.981T>G) pathogenic?

ETFA p.Thr327= (c.981T>G) is classified Likely benign in ETFA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Ultra-rare (popmax 0.0156%, eas); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFA p.Thr327= (c.981T>G)?

ETFA p.Thr327= (c.981T>G) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFA p.Thr327= (c.981T>G) in the general population?

ETFA p.Thr327= (c.981T>G) is ultra-rare (popmax 0.0156%, 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.Thr327=

c.981T>G · rs752246889 · VCV1111899

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 -0.3	GERP -3, phastCons 0.003
Overall
CADD	6.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,764 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.000503% 8/1,591,148 alleles · ultra-rare exomes 8/1,438,816 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,395
European (non-Finnish)	8.63e-05%	1,159,117

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.Thr327=
Coding: c.981T>G
MANE Select: NM_000126
dbSNP: rs752246889
Type: single nucleotide variant
Location: chr15:76216580 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.00 · 4 PDB
Residue 327: the 'domain ii' region; 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.Thr327Asn Uncertain significance ★ ⚠ same residue
MADD p.Arg327Ter Pathogenic/Likely pathogenic ★★ same residue
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

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-thr327 (accessed [today's date]).

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