Is ELAC2 p.Arg477del (c.1428AAG[1]) pathogenic?

ELAC2 p.Arg477del (c.1428AAG[1]) is classified Uncertain significance in ELAC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-06). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with ELAC2 p.Arg477del (c.1428AAG[1])?

ELAC2 p.Arg477del (c.1428AAG[1]) is associated with Inborn genetic diseases, combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Arg477del (c.1428AAG[1]) in the general population?

ELAC2 p.Arg477del (c.1428AAG[1]) is very rare (popmax 0.00167%, amr) (gnomAD).

ELAC2 p.Arg477del

c.1428AAG[1] · rs779224899 · VCV1060188

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.53	GERP -4.1, phastCons 0.031
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00136% 22/1,613,998 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.00161%	62,104
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,090

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: ELAC2
Protein: p.Arg477del
Coding: c.1428AAG[1]
MANE Select: NM_018127
dbSNP: rs779224899
Type: Microsatellite
Location: chr17:12998499 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB

Full ELAC2 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: combined oxidative phosphorylation defect type 17

Similar variants

ELAC2 p.Arg477Ser Uncertain significance ★ ⚠ same residue
ELAC2 c.2253+14_2253+15del Likely benign ★★ same condition
ELAC2 p.Glu290fs Pathogenic ★ same condition
ELAC2 p.Gly288fs Pathogenic ★ same condition
ELAC2 p.Arg465del Uncertain significance ★ same condition
ELAC2 p.Arg824fs Uncertain significance ★ same condition
ELAC2 p.Asp756fs Uncertain significance ★ same condition
ELAC2 p.Leu560del 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/elac2-p-arg477del (accessed [today's date]).

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