Is ETFB p.Pro211His (c.632C>A) pathogenic?

ETFB p.Pro211His (c.632C>A) is classified Uncertain significance in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: ambiguous (0.4865); Absent from gnomAD v4.1; Associated with multiple acyl-CoA dehydrogenase deficiency.

What condition is associated with ETFB p.Pro211His (c.632C>A)?

ETFB p.Pro211His (c.632C>A) is associated with multiple acyl-CoA dehydrogenase deficiency (ClinVar).

How common is ETFB p.Pro211His (c.632C>A) in the general population?

ETFB p.Pro211His (c.632C>A) is absent from gnomAD v4.1 (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.Pro211His (c.632C>A)?

AlphaMissense predicts ambiguous (score 0.4865) — an in-silico prediction, not a clinical call.

ETFB p.Pro211His

c.632C>A · rs760907327 · VCV847047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

multiple acyl-CoA dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.4865	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -12.83	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ETFB
Protein: p.Pro211His
Coding: c.632C>A
MANE Select: NM_001985
dbSNP: rs760907327
Type: single nucleotide variant
Location: chr19:51345347 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 211: 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.Pro211Ser Uncertain significance ★ ⚠ same residue
ETFB p.Pro211= Likely benign ★ same residue
ETFB p.Pro211fs Likely pathogenic ★★ same residue
ETFB p.Pro211Leu Uncertain significance ★ ⚠ same residue
ETFB p.Pro211Ala Likely benign ★ 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

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-pro211his (accessed [today's date]).

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