Is ETFDH p.Asp511= (c.1533T>C) pathogenic?

ETFDH p.Asp511= (c.1533T>C) is classified Benign/Likely benign in ETFDH (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-01). Rare (popmax 0.573%, nfe); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFDH p.Asp511= (c.1533T>C)?

ETFDH p.Asp511= (c.1533T>C) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFDH p.Asp511= (c.1533T>C) in the general population?

ETFDH p.Asp511= (c.1533T>C) is rare (popmax 0.573%, nfe) (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.Asp511=

c.1533T>C · rs77484245 · VCV137235

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.573%, nfe)

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 -6.2	GERP -4.4
Overall
CADD	0.966	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.573% European (non-Finnish) · 6,761/1,179,998 alleles

Filtering AF 0.562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.557%

Overall 0.601% 9,705/1,614,166 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.07%	33
European (non-Finnish)grpmax	0.573%	175
Remaining individualsnot grpmax-eligible	0.57%	176
Ashkenazi Jewishnot grpmax-eligible	0.486%	206
South Asian	0.333%	301
Admixed American	0.182%	551
African / African-American	0.0786%	1,272
Middle Eastern	0.033%	3,031
East Asian	0.00668%	14,961

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp511=
Coding: c.1533T>C
MANE Select: NM_004453
dbSNP: rs77484245
Type: single nucleotide variant
Location: chr4:158706693 (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 p.Asp511Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-asp511 (accessed [today's date]).

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