Is ELAC2 p.Arg464Trp (c.1390A>T) pathogenic?

ELAC2 p.Arg464Trp (c.1390A>T) is classified Benign/Likely benign in ELAC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1143); Rare (popmax 0.613%, eas); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Arg464Trp (c.1390A>T)?

ELAC2 p.Arg464Trp (c.1390A>T) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Arg464Trp (c.1390A>T) in the general population?

ELAC2 p.Arg464Trp (c.1390A>T) is rare (popmax 0.613%, eas) (gnomAD).

What do computational predictors say about ELAC2 p.Arg464Trp (c.1390A>T)?

AlphaMissense predicts likely benign (score 0.1143) — an in-silico prediction, not a clinical call.

ELAC2 p.Arg464Trp

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.1390A>T · rs200149324 · VCV474559

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1143 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.613%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.1143	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -8.30	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 2.1	GERP -0.37, phastCons 0.045
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	19.64	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 0.613% East Asian · 275/44,876 alleles

Filtering AF 0.553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.53%

Overall 0.018% 290/1,614,022 alleles · rare exomes 236/1,461,696 · genomes 54/152,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.613%	163
Remaining individualsnot grpmax-eligible	0.0192%	5,208
South Asian	0.0022%	45,533
European (non-Finnish)	8.47e-05%	1,180,044

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.Arg464Trp
Coding: c.1390A>T
MANE Select: NM_018127
dbSNP: rs200149324
Type: single nucleotide variant
Location: chr17:13000189 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 464: 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

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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-arg464trp (accessed [today's date]).

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