Is ETHE1 p.Phe239fs (c.717del) pathogenic?

ETHE1 p.Phe239fs (c.717del) is classified Likely pathogenic in ETHE1 (ClinVar, Single submitter, 1 submitter). Ultra-rare (gnomAD MAF 1.679e-06); Associated with ethylmalonic encephalopathy.

What condition is associated with ETHE1 p.Phe239fs (c.717del)?

ETHE1 p.Phe239fs (c.717del) is associated with ethylmalonic encephalopathy (ClinVar).

How common is ETHE1 p.Phe239fs (c.717del) in the general population?

ETHE1 p.Phe239fs (c.717del) is ultra-rare (gnomAD MAF 1.679e-06) (gnomAD).

How is Ethylmalonic encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ETHE1 p.Phe239fs

c.717del · rs2513598932 · VCV1801827

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.679e-06)

Conditions

ethylmalonic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000168% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ETHE1
Protein: p.Phe239fs
Coding: c.717del
MANE Select: NM_014297
dbSNP: rs2513598932
Type: Deletion
Location: chr19:43506898 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB
Residue 239: an α-helix

Full ETHE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Ethylmalonic encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ETHE1 p.Arg130fs Pathogenic/Likely pathogenic ★★ same condition
ETHE1 p.Gln235fs Pathogenic/Likely pathogenic ★★ same condition
ETHE1 p.Gln63fs Pathogenic/Likely pathogenic ★★ same condition
ETHE1 c.226+1del Likely pathogenic ★ same condition
ETHE1 c.82-96_119del Likely pathogenic ★ same condition
ETHE1 p.Ala21fs Pathogenic ★ same condition
ETHE1 p.Asn228_Leu229insTer Likely pathogenic ★ same condition
ETHE1 p.Asn77fs 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/ethe1-p-phe239fs (accessed [today's date]).

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