What condition is associated with COX11 p.Asp253Val (c.758A>T)?

COX11 p.Asp253Val (c.758A>T) is associated with mitochondrial complex IV deficiency, nuclear type 23 (ClinVar).

How common is COX11 p.Asp253Val (c.758A>T) in the general population?

COX11 p.Asp253Val (c.758A>T) 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.Asp253Val (c.758A>T)?

AlphaMissense predicts likely pathogenic (score 0.799) — an in-silico prediction, not a clinical call.

COX11 p.Asp253Val

Q: Is COX11 p.Asp253Val (c.758A>T) pathogenic?

COX11 p.Asp253Val (c.758A>T) is classified Uncertain significance in COX11 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.799); Absent from gnomAD v4.1; Associated with mitochondrial complex IV deficiency, nuclear type 23.

c.758A>T · VCV3377604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

mitochondrial complex IV deficiency, nuclear type 23

Computational evidence

Protein change
AlphaMissense	0.799	likely pathogenic
REVEL	0.541	indeterminate
SaProt	LLR -14.28	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,667 bp · p 0.00018 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp253Val
Coding: c.758A>T
MANE Select: NM_004375
Type: single nucleotide variant
Location: chr17:54962806 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.29

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.Ala244Pro Pathogenic ⚠ 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-asp253val (accessed [today's date]).

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