Is ELAC2 p.Ala65= (c.195G>A) pathogenic?

ELAC2 p.Ala65= (c.195G>A) is classified Conflicting classifications of pathogenicity in ELAC2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-08-24). Ultra-rare (popmax 0.0341%, nfe); Associated with combined oxidative phosphorylation defect type 17.

How common is ELAC2 p.Ala65= (c.195G>A) in the general population?

ELAC2 p.Ala65= (c.195G>A) is ultra-rare (popmax 0.0341%, nfe) (gnomAD).

ELAC2 p.Ala65=

Q: What condition is associated with ELAC2 p.Ala65= (c.195G>A)?

ELAC2 p.Ala65= (c.195G>A) is associated with combined oxidative phosphorylation defect type 17, prostate cancer, hereditary, 2 (ClinVar).

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.195G>A · rs377291764 · VCV698763

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0341%, nfe)

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.59	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.6	GERP -4
Overall
CADD	16.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0341% European (non-Finnish) · 402/1,179,496 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.0258% 416/1,611,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0341%	2,934
Remaining individualsnot grpmax-eligible	0.0144%	6,924
Finnishnot grpmax-eligible	0.00635%	15,749
African / African-American	0.00133%	75,046

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.Ala65=
Coding: c.195G>A
MANE Select: NM_018127
dbSNP: rs377291764
Type: single nucleotide variant
Location: chr17:13017753 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 65: 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

Also linked: prostate cancer, hereditary, 2

For Combined oxidative phosphorylation defect type 17 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ELAC2 p.Ala65Val 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-ala65 (accessed [today's date]).

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