Is ELAC2 p.Leu239Pro (c.716T>C) pathogenic?

ELAC2 p.Leu239Pro (c.716T>C) is classified Uncertain significance in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-13). AlphaMissense: ambiguous (0.5382); Very rare (popmax 0.00333%, amr); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Leu239Pro (c.716T>C)?

ELAC2 p.Leu239Pro (c.716T>C) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Leu239Pro (c.716T>C) in the general population?

ELAC2 p.Leu239Pro (c.716T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about ELAC2 p.Leu239Pro (c.716T>C)?

AlphaMissense predicts ambiguous (score 0.5382) — an in-silico prediction, not a clinical call.

ELAC2 p.Leu239Pro

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.716T>C · rs750047784 · VCV1374823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5382 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.5382	ambiguous
REVEL	0.527	indeterminate
SaProt	LLR -14.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,030 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,461,806 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.Leu239Pro
Coding: c.716T>C
MANE Select: NM_018127
dbSNP: rs750047784
Type: single nucleotide variant
Location: chr17:13010635 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 239: 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 p.Leu239= Likely benign ★ 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-leu239pro (accessed [today's date]).

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