Is ELAC2 p.Phe361Val (c.1081T>G) pathogenic?

ELAC2 p.Phe361Val (c.1081T>G) is classified Uncertain significance in ELAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). AlphaMissense: likely pathogenic (0.9082); Absent from gnomAD v4.1; Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Phe361Val (c.1081T>G)?

ELAC2 p.Phe361Val (c.1081T>G) is associated with combined oxidative phosphorylation defect type 17 (ClinVar).

How common is ELAC2 p.Phe361Val (c.1081T>G) in the general population?

ELAC2 p.Phe361Val (c.1081T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELAC2 p.Phe361Val (c.1081T>G)?

AlphaMissense predicts likely pathogenic (score 0.9082) — an in-silico prediction, not a clinical call.

ELAC2 p.Phe361Val

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.1081T>G · rs2508284469 · VCV1722309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.9082	likely pathogenic
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -12.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Phe361Val
Coding: c.1081T>G
MANE Select: NM_018127
dbSNP: rs2508284469
Type: single nucleotide variant
Location: chr17:13002578 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB

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.Phe361Cys 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
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-phe361val (accessed [today's date]).

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