Is COX11 p.Ala244Pro (c.730G>C) pathogenic?

COX11 p.Ala244Pro (c.730G>C) is classified Pathogenic in COX11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely pathogenic (0.7883); Absent from gnomAD v4.1; Associated with mitochondrial complex IV deficiency, nuclear type 23.

What condition is associated with COX11 p.Ala244Pro (c.730G>C)?

COX11 p.Ala244Pro (c.730G>C) is associated with mitochondrial complex IV deficiency, nuclear type 23 (ClinVar).

How common is COX11 p.Ala244Pro (c.730G>C) in the general population?

COX11 p.Ala244Pro (c.730G>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 COX11 p.Ala244Pro (c.730G>C)?

AlphaMissense predicts likely pathogenic (score 0.7883) — an in-silico prediction, not a clinical call.

COX11 p.Ala244Pro

c.730G>C · rs1269413739 · VCV2443970

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial complex IV deficiency, nuclear type 23

Computational evidence

Protein change
AlphaMissense	0.7883	likely pathogenic ✓ concordant with ClinVar
REVEL	0.162	moderately benign-leaning
SaProt	LLR -12.83	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,667 bp · p 0.00018 · regional, not allelic
Overall
CADD	29.4	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: COX11
Protein: p.Ala244Pro
Coding: c.730G>C
MANE Select: NM_004375
dbSNP: rs1269413739
Type: single nucleotide variant
Location: chr17:54962834 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.29
Residue 244: a UniProt-annotated variant site (in mc4dn23; uncertain significance; decreases respiration-derived atp levels in patient cells)

Full COX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 23 — 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

COX11 p.Asp253Val Uncertain significance ★ ⚠ same condition
COX11 p.Pro247Thr Pathogenic same condition
COX11 p.Gln223Arg Uncertain significance ⚠ same condition
COX11 p.Phe262Leu Uncertain significance ⚠ same condition
COX11 p.Arg90_Gln91insArg Uncertain significance ★ same condition
COX11 p.Thr256fs Pathogenic same condition
COX11 p.Val12fs Pathogenic same condition
COX11 p.Ala109Val Uncertain significance ★ ⚠ same type

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/cox11-p-ala244pro (accessed [today's date]).

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