Is SCO2 p.Phe67= (c.201C>T) pathogenic?

SCO2 p.Phe67= (c.201C>T) is classified Conflicting classifications of pathogenicity in SCO2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-02). Rare (popmax 0.452%, nfe); Associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1.

How common is SCO2 p.Phe67= (c.201C>T) in the general population?

SCO2 p.Phe67= (c.201C>T) is rare (popmax 0.452%, 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.Phe67=

Q: What condition is associated with SCO2 p.Phe67= (c.201C>T)?

SCO2 p.Phe67= (c.201C>T) is associated with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

c.201C>T · rs61748568 · VCV139083

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.452%, nfe)

Conditions

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

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 0.024	GERP -4.1, phastCons 0.005
Overall
CADD	5.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.452% European (non-Finnish) · 5,339/1,179,898 alleles

Filtering AF 0.442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.438%

Overall 0.366% 5,887/1,608,210 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.452%	221
Remaining individualsnot grpmax-eligible	0.307%	325
South Asian	0.223%	449
Finnishnot grpmax-eligible	0.0788%	1,269
African / African-American	0.0786%	1,272
Admixed American	0.07%	1,429
Middle Eastern	0.0499%	2,005
East Asian	0.00446%	22,436
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Phe67=
Coding: c.201C>T
MANE Select: NM_005138
dbSNP: rs61748568
Type: single nucleotide variant
Location: chr22:50524211 (GRCh38)
Gene constraint: LOEUF 1.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.14 · 1 PDB

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

Similar variants

SCO2 p.Ala74Asp Uncertain significance ★★ ⚠ same condition
SCO2 p.Arg120Trp Uncertain significance ★★ ⚠ same condition
SCO2 p.Arg206Cys Uncertain significance ★★ ⚠ same condition
SCO2 p.Arg255Gln Uncertain significance ★★ ⚠ same condition
SCO2 p.Gly129Asp Uncertain significance ★★ ⚠ same condition
SCO2 p.Gly242Arg Uncertain significance ★★ same condition
SCO2 p.Val181Ile Uncertain significance ★★ ⚠ same condition
SCO2 c.-14+522A>G Benign ★★ 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/sco2-p-phe67 (accessed [today's date]).

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