Is ECHS1 p.Lys115Gln (c.343A>C) pathogenic?

ECHS1 p.Lys115Gln (c.343A>C) is classified Conflicting classifications of pathogenicity in ECHS1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1088); Ultra-rare (popmax 0.0878%, sas); Associated with Inborn genetic diseases.

What condition is associated with ECHS1 p.Lys115Gln (c.343A>C)?

ECHS1 p.Lys115Gln (c.343A>C) is associated with Inborn genetic diseases, mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency (ClinVar).

How common is ECHS1 p.Lys115Gln (c.343A>C) in the general population?

ECHS1 p.Lys115Gln (c.343A>C) is ultra-rare (popmax 0.0878%, sas) (gnomAD).

What do computational predictors say about ECHS1 p.Lys115Gln (c.343A>C)?

AlphaMissense predicts likely benign (score 0.1088) — an in-silico prediction, not a clinical call.

ECHS1 p.Lys115Gln

c.343A>C · rs369960115 · VCV1667614

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1088 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1088	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -4.79	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 -1.4
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	0.262	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 0.0878% South Asian · 80/91,086 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0666%

Overall 0.0057% 92/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0878%	1,139
Middle Eastern	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.016%	6,247
African / African-American	0.00133%	74,930

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.Lys115Gln
Coding: c.343A>C
MANE Select: NM_004092
dbSNP: rs369960115
Type: single nucleotide variant
Location: chr10:133369975 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 115: a modified residue (n6-succinyllysine; alternate); a turn; a modified residue (n6-acetyllysine; alternate)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial short-chain Enoyl-Coa hydratase 1 deficiency

Similar variants

ECHS1 p.Lys115= Likely benign ★ 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-lys115gln (accessed [today's date]).

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