Is AARS2 c.*718C>A pathogenic?

AARS2 c.718C>A is classified Uncertain significance in AARS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-01-12). Rare (popmax 0.848%, amr); Associated with combined oxidative phosphorylation defect type 8.

What condition is associated with AARS2 c.*718C>A?

AARS2 c.*718C>A is associated with combined oxidative phosphorylation defect type 8 (ClinVar).

How common is AARS2 c.*718C>A in the general population?

AARS2 c.*718C>A is rare (popmax 0.848%, amr) (gnomAD).

AARS2 c.*718C>A

Q: How is Combined oxidative phosphorylation defect type 8 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs140359685 · VCV357042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.848%, amr)

Conditions

combined oxidative phosphorylation defect type 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.05	GERP -1.8
Non-coding constraint	Z 0.56	1 kb window · o/e 0.95 · regional · uncalibrated
Overall
CADD	1.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.848% Admixed American · 130/15,336 alleles

Filtering AF 0.729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.684%

Overall 0.485% 741/152,748 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.848%	118
European (non-Finnish)	0.746%	134
Amishnot grpmax-eligible	0.658%	152
Remaining individualsnot grpmax-eligible	0.611%	164
Middle Eastern	0.34%	294
African / African-American	0.164%	611
Ashkenazi Jewishnot grpmax-eligible	0.144%	694
South Asian	0.062%	1,613
Finnishnot grpmax-eligible	0.0377%	2,655
East Asian	0.0193%	5,194

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: AARS2
Coding: c.*718C>A
MANE Select: NM_020745
dbSNP: rs140359685
Type: single nucleotide variant
Location: chr6:44299829 (GRCh38)
Gene constraint: LOEUF 0.752 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.05 · 3 PDB

Full AARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined oxidative phosphorylation defect type 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 8 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

AARS2 c.2146-2A>G Pathogenic/Likely pathogenic ★★ same condition
AARS2 c.2255+1G>A Pathogenic ★★ same condition
AARS2 p.Arg199Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
AARS2 p.Arg521Ter Pathogenic ★★ same condition
AARS2 p.Arg592Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
AARS2 p.Arg958Ter Pathogenic/Likely pathogenic ★★ same condition
AARS2 p.Thr782Ile Likely pathogenic ★★ same condition
AARS2 p.Ala386Val Uncertain significance ★★ ⚠ 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/aars2-c-star-718c-a (accessed [today's date]).

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