Is ETFB p.Arg191Cys (c.571C>T) pathogenic?

ETFB p.Arg191Cys (c.571C>T) is classified Conflicting classifications of pathogenicity in ETFB (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-05). AlphaMissense: likely pathogenic (0.9461); Very rare (popmax 0.00818%, sas); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Arg191Cys (c.571C>T)?

ETFB p.Arg191Cys (c.571C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Arg191Cys (c.571C>T) in the general population?

ETFB p.Arg191Cys (c.571C>T) is very rare (popmax 0.00818%, sas) (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.Arg191Cys (c.571C>T)?

AlphaMissense predicts likely pathogenic (score 0.9461) — an in-silico prediction, not a clinical call.

ETFB p.Arg191Cys

c.571C>T · rs772976948 · VCV1409823

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9461 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00818%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9461	likely pathogenic
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -14.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	34.0	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 0.00818% South Asian · 7/85,600 alleles

Filtering AF 0.00379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00268%

Overall 0.00159% 25/1,567,428 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00818%	12,229
African / African-American	0.00271%	36,907
European (non-Finnish)	0.00138%	72,255

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.Arg191Cys
Coding: c.571C>T
MANE Select: NM_001985
dbSNP: rs772976948
Type: single nucleotide variant
Location: chr19:51346926 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 191: the 'recognition loop' region; 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 p.Arg191His 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.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Cys42Arg Pathogenic/Likely pathogenic ★★ same condition
ETFB p.Gln136Ter 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-arg191cys (accessed [today's date]).

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