Is ECHS1 p.Ala96= (c.288T>A) pathogenic?

ECHS1 p.Ala96= (c.288T>A) is classified Likely pathogenic in ECHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). Absent from gnomAD v4.1; Associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency.

What condition is associated with ECHS1 p.Ala96= (c.288T>A)?

ECHS1 p.Ala96= (c.288T>A) is associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (ClinVar).

How common is ECHS1 p.Ala96= (c.288T>A) in the general population?

ECHS1 p.Ala96= (c.288T>A) is absent from gnomAD v4.1 (gnomAD).

ECHS1 p.Ala96=

Q: How is Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency inherited?

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

c.288T>A · VCV3775078

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	acceptor gain · deltas
Pangolin	Δ0.83	gain · loss 0.20 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.91	phastCons 0.98
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

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: ECHS1
Protein: p.Ala96=
Coding: c.288T>A
MANE Select: NM_004092
Type: single nucleotide variant
Location: chr10:133370030 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB

Full ECHS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ECHS1 p.Ala96Val Uncertain significance ★ ⚠ same residue
ECHS1 c.414+1G>A Pathogenic/Likely pathogenic ★★ same condition
ECHS1 c.88+5G>A Pathogenic/Likely pathogenic ★★ same condition
ECHS1 p.Ala132Thr Pathogenic/Likely pathogenic ★★ same condition
ECHS1 p.Ala173Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ECHS1 p.Ala238Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
ECHS1 p.Ala278Thr Likely pathogenic ★★ same condition
ECHS1 p.Ala2Val 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/echs1-p-ala96 (accessed [today's date]).

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