Is ETFB p.Arg85Ter (c.253C>T) pathogenic?

ETFB p.Arg85Ter (c.253C>T) is classified Pathogenic/Likely pathogenic in ETFB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-04). Very rare (popmax 0.00134%, afr); Associated with ETFB-related disorder.

What condition is associated with ETFB p.Arg85Ter (c.253C>T)?

ETFB p.Arg85Ter (c.253C>T) is associated with ETFB-related disorder, multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Arg85Ter (c.253C>T) in the general population?

ETFB p.Arg85Ter (c.253C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

ETFB p.Arg85Ter

c.253C>T · rs187424345 · VCV969590

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

ETFB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
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	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,896 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,613,924 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00134%	74,896
South Asian	0.0011%	91,094
European (non-Finnish)	0.000508%	196,667

Remaining individuals 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: ETFB
Protein: p.Arg85Ter
Coding: c.253C>T
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

ETFB-related disorder

Also linked: multiple acyl-CoA dehydrogenase deficiency

Similar variants

ETFB p.Arg85Gln Uncertain significance ★★ ⚠ same residue
ETFB p.Arg85= Likely benign ★★ 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-arg85ter (accessed [today's date]).

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