Is ETFB p.Arg85= (c.253C>A) pathogenic?

ETFB p.Arg85= (c.253C>A) is classified Likely benign in ETFB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.099%, mid); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Arg85= (c.253C>A)?

ETFB p.Arg85= (c.253C>A) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Arg85= (c.253C>A) in the general population?

ETFB p.Arg85= (c.253C>A) is ultra-rare (popmax 0.099%, mid) (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

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

ETFB p.Arg85=

c.253C>A · rs187424345 · VCV788177

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

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 3	GERP 1.4, phastCons 1
Overall
CADD	16.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.00297% 48/1,614,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
Admixed American	0.0133%	7,502
African / African-American	0.00533%	18,755
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.00229%	43,703
South Asian	0.0011%	91,090

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: ETFB
Protein: p.Arg85=
Coding: c.253C>A
MANE Select: NM_001985
dbSNP: rs187424345
Type: single nucleotide variant
Location: chr19:51353254 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 85: a β-strand

Full ETFB 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

ETFB p.Arg85Ter Pathogenic/Likely pathogenic ★★ same residue
ETFB p.Arg85Gln Uncertain significance ★★ ⚠ same residue
ETFB p.Arg85Pro Uncertain significance ★ ⚠ same residue
ETFB c.375+1G>A Likely pathogenic ★★ same condition
ETFB c.375+1G>T Likely pathogenic ★★ same condition
ETFB p.Arg164Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ETFB p.Arg21Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Cys42Arg 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/etfb-p-arg85 (accessed [today's date]).

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