Is ECHS1 p.Ile152Phe (c.454A>T) pathogenic?

ECHS1 p.Ile152Phe (c.454A>T) is classified Uncertain significance in ECHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.7522); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ECHS1 p.Ile152Phe (c.454A>T)?

ECHS1 p.Ile152Phe (c.454A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ECHS1 p.Ile152Phe (c.454A>T) in the general population?

ECHS1 p.Ile152Phe (c.454A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECHS1 p.Ile152Phe (c.454A>T)?

AlphaMissense predicts likely pathogenic (score 0.7522) — an in-silico prediction, not a clinical call.

ECHS1 p.Ile152Phe

c.454A>T · VCV4246373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7522 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7522	likely pathogenic
REVEL	0.515	indeterminate
SaProt	LLR -15.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

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.Ile152Phe
Coding: c.454A>T
MANE Select: NM_004092
Type: single nucleotide variant
Location: chr10:133368983 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB
Residue 152: a β-strand

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.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
ECHS1 p.Ile165Val Uncertain significance ★★ ⚠ same condition
ECHS1 p.Ile37Thr Uncertain significance ★★ ⚠ same condition
ECHS1 c.89-6C>G Conflicting classifications of pathogenicity ★ 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-ile152phe (accessed [today's date]).

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