Is ECHS1 p.Val11Ala (c.32T>C) pathogenic?

ECHS1 p.Val11Ala (c.32T>C) is classified Benign in ECHS1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0915); Common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency.

What condition is associated with ECHS1 p.Val11Ala (c.32T>C)?

ECHS1 p.Val11Ala (c.32T>C) is associated with mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (ClinVar).

What do computational predictors say about ECHS1 p.Val11Ala (c.32T>C)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

ECHS1 p.Val11Ala

Q: How common is ECHS1 p.Val11Ala (c.32T>C) in the general population?

ECHS1 p.Val11Ala (c.32T>C) is common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.32T>C · rs10466126 · VCV1255366

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 91.8%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.90	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 0.083
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	2.63	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 91.8% East Asian · 31,951/34,808 alleles

Filtering AF 90.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 90.6%

Overall 72.9% 1,088,072/1,491,544 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	91.8%	1
Finnishnot grpmax-eligible	82.8%	1
South Asian	80.8%	1
Ashkenazi Jewishnot grpmax-eligible	77.4%	1
European (non-Finnish)	74.1%	1
Remaining individualsnot grpmax-eligible	72.3%	1
Middle Eastern	71.2%	1
Admixed American	69.1%	1
Amishnot grpmax-eligible	48.5%	2
African / African-American	31.5%	3

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.Val11Ala
Coding: c.32T>C
MANE Select: NM_004092
dbSNP: rs10466126
Type: single nucleotide variant
Location: chr10:133373302 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 11: a UniProt-annotated variant site (in)

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 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
ECHS1 p.Arg54Cys Pathogenic/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/echs1-p-val11ala (accessed [today's date]).

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