Is COX15 p.Arg71Ter (c.211C>T) pathogenic?

COX15 p.Arg71Ter (c.211C>T) is classified Conflicting classifications of pathogenicity in COX15 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-05-15). Very rare (popmax 0.00659%, sas); Associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2.

How common is COX15 p.Arg71Ter (c.211C>T) in the general population?

COX15 p.Arg71Ter (c.211C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

How is Fatal infantile cytochrome C oxidase deficiency inherited?

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

COX15 p.Arg71Ter

Q: What condition is associated with COX15 p.Arg71Ter (c.211C>T)?

COX15 p.Arg71Ter (c.211C>T) is associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 (ClinVar).

c.211C>T · rs751819645 · VCV1805694

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2

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	predicted	premature termination codon in exon 2 of 9
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.7	GERP 1.1, phastCons 1
Overall
CADD	41.0	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 0.00659% South Asian · 6/91,032 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00155% 25/1,613,652 alleles · very rare exomes 23/1,461,800 · genomes 2/151,852 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,172
Finnishnot grpmax-eligible	0.00157%	63,886
European (non-Finnish)	0.00153%	65,554

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: COX15
Protein: p.Arg71Ter
Coding: c.211C>T
MANE Select: NM_078470
dbSNP: rs751819645
Type: single nucleotide variant
Location: chr10:99729614 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.29

Full COX15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Fatal infantile cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

COX15 p.Arg71Gln Uncertain significance ★ ⚠ same residue
COX15 c.750+1G>A Likely pathogenic ★★ same condition
COX15 c.750+1G>T Likely pathogenic ★★ same condition
COX15 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same condition
COX15 p.Arg217Trp Pathogenic ★★ same condition
COX15 p.Ser151Ter Pathogenic/Likely pathogenic ★★ same condition
COX15 p.Ser229Ter Pathogenic/Likely pathogenic ★★ same condition
COX15 p.Trp102Ter 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/cox15-p-arg71ter (accessed [today's date]).

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