Is ELAC2 p.Pro300= (c.900A>G) pathogenic?

ELAC2 p.Pro300= (c.900A>G) is classified Likely benign in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.000342%); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Pro300= (c.900A>G)?

ELAC2 p.Pro300= (c.900A>G) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Pro300= (c.900A>G) in the general population?

ELAC2 p.Pro300= (c.900A>G) is very rare (popmax 0.000342%) (gnomAD).

ELAC2 p.Pro300=

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.900A>G · rs1567758616 · VCV728928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000342%)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	Δ0.77	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -3.8	GERP -4.2
Overall
CADD	3.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000342%

Overall 0.000342% 5/1,461,878 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.Pro300=
Coding: c.900A>G
MANE Select: NM_018127
dbSNP: rs1567758616
Type: single nucleotide variant
Location: chr17:13005072 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 300: 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.Pro300Ser Uncertain significance ★ ⚠ same residue
ELAC2 c.1080-1G>C Likely pathogenic ★★ same condition
ELAC2 c.1423+1G>A Pathogenic ★★ same condition
ELAC2 c.1908+1G>A Likely pathogenic ★★ same condition
ELAC2 c.245+2T>A Pathogenic/Likely pathogenic ★★ same condition
ELAC2 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same condition
ELAC2 p.Gln18Ter Pathogenic ★★ same condition
ELAC2 p.Glu30Ter Pathogenic/Likely 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-pro300 (accessed [today's date]).

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