Is ECHS1 p.Thr124fs (c.370dup) pathogenic?

ECHS1 p.Thr124fs (c.370dup) is classified Pathogenic in ECHS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-11). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with ECHS1 p.Thr124fs (c.370dup)?

ECHS1 p.Thr124fs (c.370dup) is associated with Inborn genetic diseases (ClinVar).

How common is ECHS1 p.Thr124fs (c.370dup) in the general population?

ECHS1 p.Thr124fs (c.370dup) is absent from gnomAD (gnomAD).

ECHS1 p.Thr124fs

c.370dup · rs2493842433 · VCV2032134

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	phastCons 0.92

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ECHS1
Protein: p.Thr124fs
Coding: c.370dup
MANE Select: NM_004092
dbSNP: rs2493842433
Type: Duplication
Location: chr10:133369947 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 124: an α-helix

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

Similar variants

ECHS1 p.Thr124Ile Uncertain significance ★★ ⚠ same residue
ECHS1 p.Thr124Ser Uncertain significance ★ ⚠ same residue
ECHS1 p.Thr124= Likely benign ★ same residue
ECHS1 p.Lys273Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
ECHS1 p.Ala230Ser Uncertain significance ★★ ⚠ same condition
ECHS1 p.Ala28Ser Uncertain significance ★★ ⚠ same condition
ECHS1 p.Asn245Ser Uncertain significance ★★ ⚠ same condition
ECHS1 p.Gly13Asp 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/echs1-p-thr124fs (accessed [today's date]).

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