Is COX10 p.Ala303= (c.909C>T) pathogenic?

COX10 p.Ala303= (c.909C>T) is classified Conflicting classifications of pathogenicity in COX10 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-05-01). Rare (popmax 0.965%, amr); Associated with Leigh syndrome.

What condition is associated with COX10 p.Ala303= (c.909C>T)?

COX10 p.Ala303= (c.909C>T) is associated with Leigh syndrome, mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How common is COX10 p.Ala303= (c.909C>T) in the general population?

COX10 p.Ala303= (c.909C>T) is rare (popmax 0.965%, amr) (gnomAD).

How is Leigh syndrome inherited?

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

COX10 p.Ala303=

c.909C>T · rs370260574 · VCV321816

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.965%, amr)

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 -5.8	GERP -2.8
Overall
CADD	0.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.965% Admixed American · 570/59,062 alleles

Filtering AF 0.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.874%

Overall 0.05% 807/1,612,560 alleles · rare exomes 724/1,460,518 · genomes 83/152,042 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.965%	104
East Asian	0.182%	550
South Asian	0.0604%	1,655
Middle Eastern	0.0496%	2,017
Remaining individualsnot grpmax-eligible	0.0417%	2,400
African / African-American	0.00799%	12,510
European (non-Finnish)	0.00559%	17,877

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.Ala303=
Coding: c.909C>T
MANE Select: NM_001303
dbSNP: rs370260574
Type: single nucleotide variant
Location: chr17:14192202 (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.Ala303Asp Uncertain significance ★★ ⚠ same residue
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

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-ala303 (accessed [today's date]).

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