Is COX10 p.Pro213Ser (c.637C>T) pathogenic?

COX10 p.Pro213Ser (c.637C>T) is classified Uncertain significance in COX10 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-02-07). AlphaMissense: likely pathogenic (0.8451); Absent from gnomAD v4.1; Associated with mitochondrial complex IV deficiency, nuclear type 1.

What condition is associated with COX10 p.Pro213Ser (c.637C>T)?

COX10 p.Pro213Ser (c.637C>T) is associated with mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How common is COX10 p.Pro213Ser (c.637C>T) in the general population?

COX10 p.Pro213Ser (c.637C>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 COX10 p.Pro213Ser (c.637C>T)?

AlphaMissense predicts likely pathogenic (score 0.8451) — an in-silico prediction, not a clinical call.

COX10 p.Pro213Ser

c.637C>T · rs1597527929 · VCV1030368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8451 · 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 1

Computational evidence

Protein change
AlphaMissense	0.8451	likely pathogenic
REVEL	0.692	pathogenic-leaning
SaProt	LLR -12.95	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	25.5	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: COX10
Protein: p.Pro213Ser
Coding: c.637C>T
MANE Select: NM_001303
dbSNP: rs1597527929
Type: single nucleotide variant
Location: chr17:14159889 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11

Full COX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 1 — 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

COX10 p.Pro213Leu Uncertain significance ★ ⚠ same residue
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.Val227Ile Uncertain significance ★★ ⚠ same condition
COX10 c.928+12G>A Benign/Likely benign ★★ 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-pro213ser (accessed [today's date]).

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