Is COX11 p.Val12fs (c.35_36delinsG) pathogenic?

COX11 p.Val12fs (c.3536delinsG) is classified Pathogenic in COX11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-11). Absent from gnomAD; Associated with mitochondrial complex IV deficiency, nuclear type 23.

What condition is associated with COX11 p.Val12fs (c.35_36delinsG)?

COX11 p.Val12fs (c.35_36delinsG) is associated with mitochondrial complex IV deficiency, nuclear type 23 (ClinVar).

How common is COX11 p.Val12fs (c.35_36delinsG) in the general population?

COX11 p.Val12fs (c.35_36delinsG) is absent from gnomAD (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.

COX11 p.Val12fs

c.35_36delinsG · rs2509425417 · VCV2443971

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

mitochondrial complex IV deficiency, nuclear type 23

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.3	GERP -4.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COX11
Protein: p.Val12fs
Coding: c.35_36delinsG
MANE Select: NM_004375
dbSNP: rs2509425417
Type: Indel
Location: chr17:54968611 (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.Arg90_Gln91insArg Uncertain significance ★ same condition
COX11 p.Asp253Val Uncertain significance ★ ⚠ same condition
COX11 p.Ala244Pro Pathogenic ⚠ same condition
COX11 p.Pro247Thr Pathogenic same condition
COX11 p.Thr256fs Pathogenic same condition
COX11 p.Gln223Arg Uncertain significance ⚠ same condition
COX11 p.Phe262Leu 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/cox11-p-val12fs (accessed [today's date]).

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