Is ETHE1 p.Ser119= (c.357C>T) pathogenic?

ETHE1 p.Ser119= (c.357C>T) is classified Conflicting classifications of pathogenicity in ETHE1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-19). Ultra-rare (popmax 0.0156%, eas); Associated with ethylmalonic encephalopathy.

What condition is associated with ETHE1 p.Ser119= (c.357C>T)?

ETHE1 p.Ser119= (c.357C>T) is associated with ethylmalonic encephalopathy (ClinVar).

How common is ETHE1 p.Ser119= (c.357C>T) in the general population?

ETHE1 p.Ser119= (c.357C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

How is Ethylmalonic encephalopathy inherited?

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

ETHE1 p.Ser119=

c.357C>T · rs759810296 · VCV1129307

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

ethylmalonic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -1.5, phastCons 1
Overall
CADD	11.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,880 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00155% 25/1,614,010 alleles · ultra-rare exomes 23/1,461,888 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
European (non-Finnish)	0.00153%	65,557

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: ETHE1
Protein: p.Ser119=
Coding: c.357C>T
MANE Select: NM_014297
dbSNP: rs759810296
Type: single nucleotide variant
Location: chr19:43526219 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB
Residue 119: a β-strand

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.Ser119Phe Uncertain significance ★ ⚠ same residue
ETHE1 c.505+1G>A Pathogenic ★★★ same condition
ETHE1 c.505+1G>T Pathogenic ★★★ same condition
ETHE1 p.Arg163Gln Pathogenic ★★★ same condition
ETHE1 p.Arg163Trp Pathogenic ★★★ same condition
ETHE1 p.Ala254Val Uncertain significance ★★★ ⚠ same condition
ETHE1 p.Arg124Leu Uncertain significance ★★★ ⚠ same condition
ETHE1 p.Lys66Arg Uncertain significance ★★★ ⚠ 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-ser119 (accessed [today's date]).

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