Is ELAC2 p.Arg812Trp (c.2434C>T) pathogenic?

ELAC2 p.Arg812Trp (c.2434C>T) is classified Uncertain significance in ELAC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-10). AlphaMissense: likely benign (0.1063); Ultra-rare (popmax 0.033%, mid); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Arg812Trp (c.2434C>T)?

ELAC2 p.Arg812Trp (c.2434C>T) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Arg812Trp (c.2434C>T) in the general population?

ELAC2 p.Arg812Trp (c.2434C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ELAC2 p.Arg812Trp (c.2434C>T)?

AlphaMissense predicts likely benign (score 0.1063) — an in-silico prediction, not a clinical call.

ELAC2 p.Arg812Trp

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.2434C>T · rs767611235 · VCV1504125

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1063 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.1063	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.7, phastCons 0.97
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,058 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.0026% 38/1,461,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,029
Finnishnot grpmax-eligible	0.0079%	12,659
Remaining individualsnot grpmax-eligible	0.0048%	20,833
East Asian	0.00223%	44,852
European (non-Finnish)	0.0022%	45,385
Admixed American	0.00167%	60,018

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.Arg812Trp
Coding: c.2434C>T
MANE Select: NM_018127
dbSNP: rs767611235
Type: single nucleotide variant
Location: chr17:12992865 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 812: the 'disordered' region

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.Arg812Gln Uncertain significance ★ ⚠ same residue
ELAC2 p.Arg812Leu 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

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-arg812trp (accessed [today's date]).

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