Is ECHS1 p.Ala238Val (c.713C>T) pathogenic?

ECHS1 p.Ala238Val (c.713C>T) is classified Pathogenic/Likely pathogenic in ECHS1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1955); Very rare (popmax 0.00161%, nfe); Associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency.

What condition is associated with ECHS1 p.Ala238Val (c.713C>T)?

ECHS1 p.Ala238Val (c.713C>T) is associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (ClinVar).

How common is ECHS1 p.Ala238Val (c.713C>T) in the general population?

ECHS1 p.Ala238Val (c.713C>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about ECHS1 p.Ala238Val (c.713C>T)?

AlphaMissense predicts likely benign (score 0.1955) — an in-silico prediction, not a clinical call.

ECHS1 p.Ala238Val

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.713C>T · rs200584793 · VCV972723

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

Computational evidence

Protein change
AlphaMissense	0.1955	likely benign ⚠ discordant with ClinVar
REVEL	0.261	benign-leaning
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	phastCons 0.65
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	19.36	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,016 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00144% 21/1,461,556 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,506
South Asian	0.0011%	91,092

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: ECHS1
Protein: p.Ala238Val
Coding: c.713C>T
MANE Select: NM_004092
dbSNP: rs200584793
Type: single nucleotide variant
Location: chr10:133366002 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 238: an α-helix

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.Ala238Thr Likely pathogenic ★ same residue
ECHS1 p.Ala238Pro Conflicting classifications of pathogenicity ★ ⚠ 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.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-ala238val (accessed [today's date]).

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