Is COX10 p.Pro233= (c.699A>G) pathogenic?

COX10 p.Pro233= (c.699A>G) is classified Benign in COX10 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-11-28). Common (popmax 60.2%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Leigh syndrome.

What condition is associated with COX10 p.Pro233= (c.699A>G)?

COX10 p.Pro233= (c.699A>G) is associated with Leigh syndrome, mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How is Leigh syndrome inherited?

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

COX10 p.Pro233=

Q: How common is COX10 p.Pro233= (c.699A>G) in the general population?

COX10 p.Pro233= (c.699A>G) is common (popmax 60.2%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.699A>G · rs2230354 · VCV136995

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 60.2%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Leigh syndrome

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 -20	GERP -3
Overall
CADD	0.006	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.2% South Asian · 54,809/91,010 alleles

Filtering AF 59.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.6%

Overall 58.6% 944,231/1,611,018 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	62%	2
Ashkenazi Jewishnot grpmax-eligible	60.8%	2
South Asiangrpmax	60.2%	2
European (non-Finnish)	59.2%	2
Remaining individualsnot grpmax-eligible	58.5%	2
Amishnot grpmax-eligible	58.2%	2
Admixed American	57.4%	2
East Asian	56%	2
Middle Eastern	55.2%	2
African / African-American	47.2%	2

Finnish 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: COX10
Protein: p.Pro233=
Coding: c.699A>G
MANE Select: NM_001303
dbSNP: rs2230354
Type: single nucleotide variant
Location: chr17:14191992 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11

Full COX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Leigh syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial complex IV deficiency, nuclear type 1

For Leigh syndrome (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance, X-linked recessive
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same condition
COX10 c.-89G>C Uncertain significance ★★ same condition
COX10 c.-89G>T Uncertain significance ★★ same condition
COX10 p.Ala390Val Uncertain significance ★★ ⚠ same condition
COX10 p.Arg354Gln Uncertain significance ★★ ⚠ same condition
COX10 p.Arg355His Uncertain significance ★★ ⚠ same condition
COX10 p.Arg398Cys Uncertain significance ★★ ⚠ same condition
COX10 p.Asp132Tyr Uncertain significance ★★ ⚠ 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/cox10-p-pro233 (accessed [today's date]).

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