Is ETHE1 p.Val8fs (c.19_20dup) pathogenic?

ETHE1 p.Val8fs (c.1920dup) is classified Pathogenic in ETHE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). No gnomAD frequency available for this variant; Associated with ethylmalonic encephalopathy.

What condition is associated with ETHE1 p.Val8fs (c.19_20dup)?

ETHE1 p.Val8fs (c.19_20dup) is associated with ethylmalonic encephalopathy (ClinVar).

How common is ETHE1 p.Val8fs (c.19_20dup) in the general population?

ETHE1 p.Val8fs (c.19_20dup) is no gnomAD frequency available for this variant (gnomAD).

How is Ethylmalonic encephalopathy inherited?

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

ETHE1 p.Val8fs

c.19_20dup · rs2513631762 · VCV2734186

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.042	GERP -2.3

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ETHE1
Protein: p.Val8fs
Coding: c.19_20dup
MANE Select: NM_014297
dbSNP: rs2513631762
Type: Duplication
Location: chr19:43527157 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB

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.Val8= Likely benign ★ same residue
ETHE1 p.Val202fs Pathogenic ★★★ same condition
ETHE1 p.Tyr74Ter Pathogenic ★★ same condition
ETHE1 p.Ala155fs Pathogenic ★ same condition
ETHE1 p.Arg214fs Likely pathogenic ★ same condition
ETHE1 p.Glu56_Thr57insIleLeuGlu Likely pathogenic ★ same condition
ETHE1 p.Gly87fs Pathogenic ★ same condition
ETHE1 p.Ile182fs 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-val8fs (accessed [today's date]).

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