Is COX10 p.Thr28Ile (c.83C>T) pathogenic?

COX10 p.Thr28Ile (c.83C>T) is classified Benign/Likely benign in COX10 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0841); Common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Leigh syndrome.

What condition is associated with COX10 p.Thr28Ile (c.83C>T)?

COX10 p.Thr28Ile (c.83C>T) 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.

What do computational predictors say about COX10 p.Thr28Ile (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

COX10 p.Thr28Ile

Q: How common is COX10 p.Thr28Ile (c.83C>T) in the general population?

COX10 p.Thr28Ile (c.83C>T) is common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.83C>T · rs16948978 · VCV137004

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Leigh syndrome

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.008	GERP -1.9
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.97 · regional, not allelic
Overall
CADD	9.803	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.4% African / African-American · 4,797/75,004 alleles

Filtering AF 6.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.18%

Overall 0.348% 5,619/1,614,028 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.4%	16
Remaining individualsnot grpmax-eligible	0.531%	188
Admixed American	0.437%	229
Ashkenazi Jewishnot grpmax-eligible	0.28%	357
Middle Eastern	0.181%	551
European (non-Finnish)	0.0107%	9,365
South Asian	0.00878%	11,385

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.Thr28Ile
Coding: c.83C>T
MANE Select: NM_001303
dbSNP: rs16948978
Type: single nucleotide variant
Location: chr17:14074362 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11
Residue 28: a UniProt-annotated variant site (in)

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-thr28ile (accessed [today's date]).

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