Is SCO2 p.Ser246= (c.738G>C) pathogenic?

SCO2 p.Ser246= (c.738G>C) is classified Conflicting classifications of pathogenicity in SCO2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.042%, nfe); Associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1.

How common is SCO2 p.Ser246= (c.738G>C) in the general population?

SCO2 p.Ser246= (c.738G>C) is ultra-rare (popmax 0.042%, 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.Ser246=

Q: What condition is associated with SCO2 p.Ser246= (c.738G>C)?

SCO2 p.Ser246= (c.738G>C) is associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

c.738G>C · rs200605042 · VCV342123

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.042%, 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
Constraint at this position
Conservation	phyloP -13	GERP -4
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.042% European (non-Finnish) · 496/1,180,042 alleles

Filtering AF 0.0389% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0377%

Overall 0.0327% 528/1,613,940 alleles · ultra-rare exomes 508/1,461,760 · genomes 20/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.042%	2,379
Remaining individualsnot grpmax-eligible	0.0368%	2,717
African / African-American	0.00667%	14,982
Admixed American	0.00333%	30,004
South Asian	0.0022%	45,543

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.Ser246=
Coding: c.738G>C
MANE Select: NM_005138
dbSNP: rs200605042
Type: single nucleotide variant
Location: chr22:50523674 (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

Also linked: mitochondrial complex IV deficiency, nuclear type 1

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-ser246 (accessed [today's date]).

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