Is ELAC2 p.Asp756fs (c.2266_2267del) pathogenic?

ELAC2 p.Asp756fs (c.22662267del) is classified Uncertain significance in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Very rare (popmax 0.00017%, nfe); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Asp756fs (c.2266_2267del)?

ELAC2 p.Asp756fs (c.2266_2267del) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Asp756fs (c.2266_2267del) in the general population?

ELAC2 p.Asp756fs (c.2266_2267del) is very rare (popmax 0.00017%, nfe) (gnomAD).

ELAC2 p.Asp756fs

Q: How is Combined oxidative phosphorylation defect type 17 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2266_2267del · rs2040267666 · VCV847719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (24 of 24) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP -0.11, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,762 alleles

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

Overall 0.000138% 2/1,451,414 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: ELAC2
Protein: p.Asp756fs
Coding: c.2266_2267del
MANE Select: NM_018127
dbSNP: rs2040267666
Type: Microsatellite
Location: chr17:12993032 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 756: an α-helix

Full ELAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation defect type 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 17 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ELAC2 p.Arg477del Uncertain significance ★★ same condition
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.Leu560del Uncertain significance ★ same condition
ELAC2 p.Lys822del 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-asp756fs (accessed [today's date]).

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