Is ETFB p.Pro211Leu (c.632C>T) pathogenic?

ETFB p.Pro211Leu (c.632C>T) is classified Uncertain significance in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.1786); Very rare (popmax 8.47e-05%, nfe).

How common is ETFB p.Pro211Leu (c.632C>T) in the general population?

ETFB p.Pro211Leu (c.632C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ETFB p.Pro211Leu (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1786) — an in-silico prediction, not a clinical call.

ETFB p.Pro211Leu

c.632C>T · rs760907327 · VCV3251391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1786	likely benign
REVEL	0.356	indeterminate
SaProt	LLR -12.28	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 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	24.1	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 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.84e-05% 1/1,461,884 alleles · very rare

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.Pro211Leu
Coding: c.632C>T
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

Similar variants

ETFB p.Pro211His Uncertain significance ★ ⚠ same residue
ETFB p.Pro211Ser Uncertain significance ★ ⚠ same residue
ETFB p.Pro211= Likely benign ★ same residue
ETFB p.Pro211Ala Likely benign ★ same residue
ETFB p.Pro211fs Likely pathogenic ★★ same residue
ETFB c.375+1G>A Likely pathogenic ★★ same type
ETFB c.375+1G>T Likely pathogenic ★★ same type
ETFB p.Arg164Gln Pathogenic/Likely pathogenic ★★ ⚠ same type

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-pro211leu (accessed [today's date]).

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