Is SCO2 p.Arg79= (c.237G>A) pathogenic?

SCO2 p.Arg79= (c.237G>A) is classified Conflicting classifications of pathogenicity in SCO2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0483%, amr); Associated with mitochondrial DNA depletion syndrome 1.

What condition is associated with SCO2 p.Arg79= (c.237G>A)?

SCO2 p.Arg79= (c.237G>A) is associated with mitochondrial DNA depletion syndrome 1, cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (ClinVar).

How common is SCO2 p.Arg79= (c.237G>A) in the general population?

SCO2 p.Arg79= (c.237G>A) is ultra-rare (popmax 0.0483%, amr) (gnomAD).

SCO2 p.Arg79=

Q: How is Mitochondrial neurogastrointestinal encephalomyopathy inherited?

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

c.237G>A · rs150485659 · VCV342126

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 0.0483%, amr)

Conditions

mitochondrial DNA depletion syndrome 1

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 -0.41	GERP -2.8
Overall
CADD	2.531	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0483% Admixed American · 29/60,024 alleles

Filtering AF 0.0345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0299%

Overall 0.0221% 356/1,610,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.703%	142
Remaining individualsnot grpmax-eligible	0.0641%	1,561
Admixed Americangrpmax	0.0483%	2,070
Middle Eastern	0.0166%	6,022
Finnishnot grpmax-eligible	0.00832%	12,016
African / African-American	0.00666%	15,010
European (non-Finnish)	0.00576%	17,353

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg79=
Coding: c.237G>A
MANE Select: NM_152299 · reported on NM_005138
dbSNP: rs150485659
Type: single nucleotide variant
Location: chr22:50524175 (GRCh38)

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

Disease context

mitochondrial DNA depletion syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1

For Mitochondrial neurogastrointestinal encephalomyopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Europe)

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-arg79 (accessed [today's date]).

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