Is ELAC2 p.Ser736fs (c.2207del) pathogenic?

ELAC2 p.Ser736fs (c.2207del) is classified Pathogenic in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-08). Very rare (popmax 8.47e-05%, nfe); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Ser736fs (c.2207del)?

ELAC2 p.Ser736fs (c.2207del) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Ser736fs (c.2207del) in the general population?

ELAC2 p.Ser736fs (c.2207del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ELAC2 p.Ser736fs

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.2207del · VCV4763839

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 within the last 50 nt of the penultimate exon (23 of 24, 46 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP -0.028, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,892 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.Ser736fs
Coding: c.2207del
MANE Select: NM_018127
Type: Deletion
Location: chr17:12993733 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 736: a modified residue (phosphoserine)

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.Cys670fs Pathogenic ★★ same condition
ELAC2 p.Ile153fs Pathogenic ★★ same condition
ELAC2 p.Met715fs Pathogenic/Likely pathogenic ★★ same condition
ELAC2 c.432+1del Uncertain significance ★★ same condition
ELAC2 c.797+14del Benign/Likely benign ★★ same condition
ELAC2 c.2109-6_2111del Likely pathogenic ★ same condition
ELAC2 p.Ala11fs Pathogenic ★ same condition
ELAC2 p.Cys405fs Pathogenic ★ 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-ser736fs (accessed [today's date]).

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