Is ELAC2 p.Pro32Arg (c.95C>G) pathogenic?

ELAC2 p.Pro32Arg (c.95C>G) is classified Benign/Likely benign in ELAC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.1139); Rare (popmax 0.578%, amr); Associated with combined oxidative phosphorylation defect type 17.

What condition is associated with ELAC2 p.Pro32Arg (c.95C>G)?

ELAC2 p.Pro32Arg (c.95C>G) is associated with combined oxidative phosphorylation defect type 17, ovarian cancer (ClinVar).

How common is ELAC2 p.Pro32Arg (c.95C>G) in the general population?

ELAC2 p.Pro32Arg (c.95C>G) is rare (popmax 0.578%, amr) (gnomAD).

What do computational predictors say about ELAC2 p.Pro32Arg (c.95C>G)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

ELAC2 p.Pro32Arg

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.95C>G · rs544551424 · VCV384867

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.578%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 17

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -6.44	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 6.2	GERP 1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 25 kb · p 0.4 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.578% Admixed American · 308/53,248 alleles

Filtering AF 0.525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.504%

Overall 0.0273% 427/1,565,726 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.578%	173
East Asian	0.191%	523
Remaining individualsnot grpmax-eligible	0.033%	3,030
African / African-American	0.0176%	5,684
South Asian	0.00116%	86,354
European (non-Finnish)	0.000346%	289,409

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.Pro32Arg
Coding: c.95C>G
MANE Select: NM_018127
dbSNP: rs544551424
Type: single nucleotide variant
Location: chr17:13017853 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81 · 10 PDB
Residue 32: 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

Also linked: ovarian cancer

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-pro32arg (accessed [today's date]).

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