Is COX10 p.Asp336Val (c.1007A>T) pathogenic?

COX10 p.Asp336Val (c.1007A>T) is classified Pathogenic/Likely pathogenic in COX10 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-14). AlphaMissense: likely pathogenic (0.9961); Ultra-rare (popmax 0.017%, nfe); Associated with mitochondrial complex IV deficiency, nuclear type 3.

What condition is associated with COX10 p.Asp336Val (c.1007A>T)?

COX10 p.Asp336Val (c.1007A>T) is associated with mitochondrial complex IV deficiency, nuclear type 3, mitochondrial complex IV deficiency, nuclear type 1 (ClinVar).

How common is COX10 p.Asp336Val (c.1007A>T) in the general population?

COX10 p.Asp336Val (c.1007A>T) is ultra-rare (popmax 0.017%, nfe) (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.Asp336Val (c.1007A>T)?

AlphaMissense predicts likely pathogenic (score 0.9961) — an in-silico prediction, not a clinical call.

COX10 p.Asp336Val

c.1007A>T · rs104894557 · VCV7525

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely pathogenic

0.9961 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial complex IV deficiency, nuclear type 3

Computational evidence

Protein change
AlphaMissense	0.9961	likely pathogenic ✓ concordant with ClinVar · top 3% in COX10
REVEL	0.984	strongly pathogenic-leaning
SaProt	LLR -13.14	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 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 372 bp · p 0.13 · regional, not allelic
Overall
CADD	31.0	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

Grpmax group 0.017% European (non-Finnish) · 201/1,179,966 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.0128% 206/1,614,004 alleles · ultra-rare exomes 196/1,461,752 · genomes 10/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.017%	5,870
African / African-American	0.004%	25,013
Admixed American	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,498

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COX10
Protein: p.Asp336Val
Coding: c.1007A>T
MANE Select: NM_001303
dbSNP: rs104894557
Type: single nucleotide variant
Location: chr17:14206888 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.11
Residue 336: a UniProt-annotated variant site (in mc4dn3)

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

Disease context

mitochondrial complex IV deficiency, nuclear type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial complex IV deficiency, nuclear type 1

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX10 p.Asp336Gly Pathogenic same residue
COX10 p.Gln230Ter Likely pathogenic ★★ same condition
COX10 p.Pro225Leu Likely pathogenic ★★ same condition
COX10 c.-89G>C Uncertain significance ★★ same condition
COX10 c.-89G>T Uncertain significance ★★ same condition
COX10 p.Ala174Thr Uncertain significance ★★ ⚠ same condition
COX10 p.Ala175Val Uncertain significance ★★ ⚠ same condition
COX10 p.Ala261Ser 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/cox10-p-asp336val (accessed [today's date]).

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