Is ETFB p.Arg106Trp (c.316C>T) pathogenic?

ETFB p.Arg106Trp (c.316C>T) is classified Conflicting classifications of pathogenicity in ETFB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-24). AlphaMissense: likely benign (0.2561); Ultra-rare (popmax 0.0333%, amr); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Arg106Trp (c.316C>T)?

ETFB p.Arg106Trp (c.316C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Arg106Trp (c.316C>T) in the general population?

ETFB p.Arg106Trp (c.316C>T) is ultra-rare (popmax 0.0333%, amr) (gnomAD).

How is Multiple acyl-CoA dehydrogenase deficiency inherited?

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

What do computational predictors say about ETFB p.Arg106Trp (c.316C>T)?

AlphaMissense predicts likely benign (score 0.2561) — an in-silico prediction, not a clinical call.

ETFB p.Arg106Trp

c.316C>T · rs748730384 · VCV1371587

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2561 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.2561	likely benign
REVEL	0.607	indeterminate
SaProt	LLR -13.72	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 0.25, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% Admixed American · 20/60,010 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0184%

Overall 0.0026% 42/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0333%	3,000
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00267%	37,463
South Asian	0.0022%	45,546
European (non-Finnish)	0.000932%	107,274

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.Arg106Trp
Coding: c.316C>T
MANE Select: NM_001985
dbSNP: rs748730384
Type: single nucleotide variant
Location: chr19:51353191 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 106: an α-helix

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 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.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Cys42Arg Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Gln136Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Glu60Ter 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-arg106trp (accessed [today's date]).

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