Is ELAC2 p.Ser507= (c.1521C>T) pathogenic?

ELAC2 p.Ser507= (c.1521C>T) is classified Conflicting classifications of pathogenicity in ELAC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-07-18). Ultra-rare (popmax 0.0165%, mid); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Ser507= (c.1521C>T)?

ELAC2 p.Ser507= (c.1521C>T) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Ser507= (c.1521C>T) in the general population?

ELAC2 p.Ser507= (c.1521C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ELAC2 p.Ser507=

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.1521C>T · rs772549996 · VCV515748

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.92, phastCons 1
Overall
CADD	9.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000558% 9/1,613,158 alleles · ultra-rare exomes 9/1,460,864 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Admixed American	0.0133%	7,497

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.Ser507=
Coding: c.1521C>T
MANE Select: NM_018127
dbSNP: rs772549996
Type: single nucleotide variant
Location: chr17:12996685 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 507: 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-ser507 (accessed [today's date]).

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