Is ETFB p.Ser151Phe (c.452C>T) pathogenic?

ETFB p.Ser151Phe (c.452C>T) is classified Conflicting classifications of pathogenicity in ETFB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). AlphaMissense: ambiguous (0.5396); Rare (popmax 0.675%, eas); Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Ser151Phe (c.452C>T)?

ETFB p.Ser151Phe (c.452C>T) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Ser151Phe (c.452C>T) in the general population?

ETFB p.Ser151Phe (c.452C>T) is rare (popmax 0.675%, eas) (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.Ser151Phe (c.452C>T)?

AlphaMissense predicts ambiguous (score 0.5396) — an in-silico prediction, not a clinical call.

ETFB p.Ser151Phe

c.452C>T · rs74735908 · VCV697821

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5396 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.675%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.5396	ambiguous
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -15.56	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	33.0	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 0.675% East Asian · 303/44,868 alleles

Filtering AF 0.613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.588%

Overall 0.0212% 342/1,614,022 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.675%	148
Remaining individualsnot grpmax-eligible	0.024%	4,167
South Asian	0.011%	9,105
Admixed American	0.00167%	60,004
European (non-Finnish)	0.0011%	90,769

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.Ser151Phe
Coding: c.452C>T
MANE Select: NM_001985
dbSNP: rs74735908
Type: single nucleotide variant
Location: chr19:51347045 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 151: 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 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-ser151phe (accessed [today's date]).

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