Is ECHS1 p.Gly89Val (c.266G>T) pathogenic?

ECHS1 p.Gly89Val (c.266G>T) is classified Uncertain significance in ECHS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely pathogenic (0.9455); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ECHS1 p.Gly89Val (c.266G>T)?

ECHS1 p.Gly89Val (c.266G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ECHS1 p.Gly89Val (c.266G>T) in the general population?

ECHS1 p.Gly89Val (c.266G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ECHS1 p.Gly89Val (c.266G>T)?

AlphaMissense predicts likely pathogenic (score 0.9455) — an in-silico prediction, not a clinical call.

ECHS1 p.Gly89Val

c.266G>T · VCV3506479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9455	likely pathogenic
REVEL	0.616	indeterminate
SaProt	LLR -18.62	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 7.5	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	24.8	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

Grpmax group 0.00017% European (non-Finnish) · 2/1,173,750 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,599,340 alleles · very rare

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.Gly89Val
Coding: c.266G>T
MANE Select: NM_004092
Type: single nucleotide variant
Location: chr10:133370580 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB

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.Gly89= 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
ECHS1 p.Ile165Val Uncertain significance ★★ ⚠ same condition
ECHS1 p.Ile37Thr 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-gly89val (accessed [today's date]).

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