Is COX16 p.Arg82Ter (c.244C>T) pathogenic?

COX16 p.Arg82Ter (c.244C>T) is classified Pathogenic in COX16 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-04). Ultra-rare (popmax 0.0106%, nfe); Associated with mitochondrial complex IV deficiency, nuclear type 22.

What condition is associated with COX16 p.Arg82Ter (c.244C>T)?

COX16 p.Arg82Ter (c.244C>T) is associated with mitochondrial complex IV deficiency, nuclear type 22 (ClinVar).

How common is COX16 p.Arg82Ter (c.244C>T) in the general population?

COX16 p.Arg82Ter (c.244C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

How is Isolated cytochrome C oxidase deficiency inherited?

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

COX16 p.Arg82Ter

c.244C>T · rs781059799 · VCV1120203

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Conditions

mitochondrial complex IV deficiency, nuclear type 22

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.014, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 124/1,171,842 alleles

Filtering AF 0.00907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00848%

Overall 0.00795% 127/1,596,628 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,450
Remaining individualsnot grpmax-eligible	0.00325%	30,771
South Asian	0.00114%	87,850

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: COX16
Protein: p.Arg82Ter
Coding: c.244C>T
MANE Select: NM_016468
dbSNP: rs781059799
Type: single nucleotide variant
Location: chr14:70326410 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50
Residue 82: the 'disordered' region; a UniProt-annotated variant site (in mc4dn22; isolated complex iv deficiency in homozygous patient cells)

Full COX16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX16 c.141+10A>G Uncertain significance ★ same condition
COX16 p.Leu63fs Likely pathogenic ★ same condition
COX16 p.Ser62Pro Uncertain significance ★★ ⚠ same type
COX16 p.Arg11Leu Uncertain significance ★ ⚠ same type
COX16 p.Arg34His Uncertain significance ★ ⚠ same type
COX16 p.Asn80Asp Uncertain significance ★ ⚠ same type
COX16 p.Gly17Ser Uncertain significance ★ ⚠ same type
COX16 p.Ile70Met Uncertain significance ★ ⚠ same type

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/cox16-p-arg82ter (accessed [today's date]).

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