Is ETFDH p.Asp517Val (c.1550A>T) pathogenic?

ETFDH p.Asp517Val (c.1550A>T) is classified Uncertain significance in ETFDH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely pathogenic (0.958); Absent from gnomAD v4.1; Associated with myopathy.

What condition is associated with ETFDH p.Asp517Val (c.1550A>T)?

ETFDH p.Asp517Val (c.1550A>T) is associated with myopathy (ClinVar).

How common is ETFDH p.Asp517Val (c.1550A>T) in the general population?

ETFDH p.Asp517Val (c.1550A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ETFDH p.Asp517Val (c.1550A>T)?

AlphaMissense predicts likely pathogenic (score 0.958) — an in-silico prediction, not a clinical call.

ETFDH p.Asp517Val

c.1550A>T · rs777302338 · VCV1801699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.958 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myopathy

Computational evidence

Protein change
AlphaMissense	0.958	likely pathogenic
REVEL	0.991	strongly pathogenic-leaning
SaProt	LLR -16.08	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 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,312 bp · p 0.11 · regional, not allelic
Overall
CADD	28.7	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: ETFDH
Protein: p.Asp517Val
Coding: c.1550A>T
MANE Select: NM_004453
dbSNP: rs777302338
Type: single nucleotide variant
Location: chr4:158706710 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.60

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

Disease context

myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ETFDH p.Tyr304Cys Uncertain significance ★ ⚠ same condition
ETFDH c.1116+2T>C Likely pathogenic ★★ same type
ETFDH c.1117-1G>A Likely pathogenic ★★ same type
ETFDH c.1117-2A>G Pathogenic/Likely pathogenic ★★ same type
ETFDH c.1285+1G>A Pathogenic ★★ same type
ETFDH c.1469-1G>T Likely pathogenic ★★ same type
ETFDH c.1690+1G>T Pathogenic ★★ same type
ETFDH c.1690+2T>G 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/etfdh-p-asp517val (accessed [today's date]).

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