Is COX20 p.Thr52Pro (c.154A>C) pathogenic?

COX20 p.Thr52Pro (c.154A>C) is classified Pathogenic in COX20 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-01-01). AlphaMissense: likely pathogenic (0.6891); Absent from gnomAD v4.1; Associated with mitochondrial complex IV deficiency, nuclear type 11.

What condition is associated with COX20 p.Thr52Pro (c.154A>C)?

COX20 p.Thr52Pro (c.154A>C) is associated with mitochondrial complex IV deficiency, nuclear type 11 (ClinVar).

How common is COX20 p.Thr52Pro (c.154A>C) in the general population?

COX20 p.Thr52Pro (c.154A>C) is absent from gnomAD v4.1 (gnomAD).

How is Isolated cytochrome C oxidase deficiency inherited?

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

What do computational predictors say about COX20 p.Thr52Pro (c.154A>C)?

AlphaMissense predicts likely pathogenic (score 0.6891) — an in-silico prediction, not a clinical call.

COX20 p.Thr52Pro

c.154A>C · rs587777004 · VCV55889

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial complex IV deficiency, nuclear type 11

Computational evidence

Protein change
AlphaMissense	0.6891	likely pathogenic ✓ concordant with ClinVar
REVEL	0.665	pathogenic-leaning
SaProt	LLR -11.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 7,458 bp · p 0.56 · regional, not allelic
Overall
CADD	27.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COX20
Protein: p.Thr52Pro
Coding: c.154A>C
MANE Select: NM_198076
dbSNP: rs587777004
Type: single nucleotide variant
Location: chr1:244842055 (GRCh38)
Gene constraint: LOEUF 1.927 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.42
Residue 52: a UniProt-annotated variant site (in mc4dn11; reduced protein expression; defective mitochondrial respiratory chain complex iv assembly; decreased interaction with mt-co2/cox2; increased interaction with tmem177)

Full COX20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX20 c.157+3G>C Pathogenic/Likely pathogenic ★★ same condition
COX20 p.Lys14Arg Pathogenic ★★ ⚠ same condition
COX20 p.Tyr36Ter Likely pathogenic ★★ same condition
COX20 p.Ala3Thr Uncertain significance ★★ ⚠ same condition
COX20 p.Arg31Trp Uncertain significance ★★ ⚠ same condition
COX20 p.Asp107Asn Uncertain significance ★★ ⚠ same condition
COX20 p.Asp107His Uncertain significance ★★ same condition
COX20 p.Cys59Arg 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/cox20-p-thr52pro (accessed [today's date]).

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