Is SCO2 p.Arg255= (c.763C>A) pathogenic?

SCO2 p.Arg255= (c.763C>A) is classified Benign/Likely benign in SCO2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.08%, nfe); Associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1.

How common is SCO2 p.Arg255= (c.763C>A) in the general population?

SCO2 p.Arg255= (c.763C>A) is low-frequency (popmax 1.08%, nfe) (gnomAD).

How is Fatal infantile cytochrome C oxidase deficiency inherited?

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

SCO2 p.Arg255=

Q: What condition is associated with SCO2 p.Arg255= (c.763C>A)?

SCO2 p.Arg255= (c.763C>A) is associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (ClinVar).

c.763C>A · rs112793292 · VCV139087

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, nfe)

Conditions

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.29	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP 2.7	GERP -4, phastCons 0.77
Overall
CADD	1.211	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% European (non-Finnish) · 12,739/1,180,022 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.869% 14,019/1,613,860 alleles · low-frequency exomes 13,141/1,461,532 · genomes 878/152,328 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.787%	127
Finnishnot grpmax-eligible	0.353%	284
Ashkenazi Jewishnot grpmax-eligible	0.331%	302
Admixed American	0.273%	366
South Asian	0.193%	518
Middle Eastern	0.184%	545
African / African-American	0.151%	664
Amishnot grpmax-eligible	0.11%	910

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: SCO2
Protein: p.Arg255=
Coding: c.763C>A
MANE Select: NM_005138
dbSNP: rs112793292
Type: single nucleotide variant
Location: chr22:50523649 (GRCh38)

Full SCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 — 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

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/sco2-p-arg255 (accessed [today's date]).

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