Is ETFB p.Arg85Pro (c.254G>C) pathogenic?

ETFB p.Arg85Pro (c.254G>C) is classified Uncertain significance in ETFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.9874); Absent from gnomAD v4.1.

How common is ETFB p.Arg85Pro (c.254G>C) in the general population?

ETFB p.Arg85Pro (c.254G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ETFB p.Arg85Pro (c.254G>C)?

AlphaMissense predicts likely pathogenic (score 0.9874) — an in-silico prediction, not a clinical call.

ETFB p.Arg85Pro

c.254G>C · rs747881617 · VCV2683519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9874 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9874	likely pathogenic · top 7% in ETFB
REVEL	0.887	moderately pathogenic-leaning
SaProt	LLR -16.31	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 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 21 kb · p 0.0022 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Arg85Pro
Coding: c.254G>C
MANE Select: NM_001985
dbSNP: rs747881617
Type: single nucleotide variant
Location: chr19:51353253 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.19 · 4 PDB
Residue 85: a β-strand

Full ETFB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ETFB p.Arg85Ter Pathogenic/Likely pathogenic ★★ same residue
ETFB p.Arg85Gln Uncertain significance ★★ ⚠ same residue
ETFB p.Arg85= Likely benign ★★ 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
ETFB p.Arg21Ter Pathogenic/Likely pathogenic ★★ same type
ETFB p.Cys42Arg 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-arg85pro (accessed [today's date]).

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