Is ELAC2 p.Leu599Pro (c.1796T>C) pathogenic?

ELAC2 p.Leu599Pro (c.1796T>C) is classified Uncertain significance in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-29). AlphaMissense: likely benign (0.3368); Absent from gnomAD v4.1; Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Leu599Pro (c.1796T>C)?

ELAC2 p.Leu599Pro (c.1796T>C) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Leu599Pro (c.1796T>C) in the general population?

ELAC2 p.Leu599Pro (c.1796T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELAC2 p.Leu599Pro (c.1796T>C)?

AlphaMissense predicts likely benign (score 0.3368) — an in-silico prediction, not a clinical call.

ELAC2 p.Leu599Pro

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.1796T>C · rs2143561613 · VCV1383802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3368 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.3368	likely benign
REVEL	0.487	indeterminate
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELAC2
Protein: p.Leu599Pro
Coding: c.1796T>C
MANE Select: NM_018127
dbSNP: rs2143561613
Type: single nucleotide variant
Location: chr17:12995715 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 599: 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

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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-leu599pro (accessed [today's date]).

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