Is ELAC2 p.Ile484= (c.1452C>A) pathogenic?

ELAC2 p.Ile484= (c.1452C>A) is classified Likely benign in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Very rare (popmax 0.00223%, eas); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Ile484= (c.1452C>A)?

ELAC2 p.Ile484= (c.1452C>A) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Ile484= (c.1452C>A) in the general population?

ELAC2 p.Ile484= (c.1452C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

ELAC2 p.Ile484=

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.1452C>A · rs1422432399 · VCV2801409

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.157	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.27 · evaluated, not missing
Pangolin	Δ0.22	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 3.4	GERP 2.1, phastCons 1
Overall
CADD	7.683	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Overall 6.19e-05% 1/1,614,208 alleles · very rare exomes 1/1,461,858 · genomes 0/152,350 · joint denominator

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.Ile484=
Coding: c.1452C>A
MANE Select: NM_018127
dbSNP: rs1422432399
Type: single nucleotide variant
Location: chr17:12998480 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 484: a β-strand

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 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
ELAC2 p.Glu482Ter 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-ile484 (accessed [today's date]).

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