Is COX10 p.Ser200Tyr (c.599C>A) pathogenic?

COX10 p.Ser200Tyr (c.599C>A) is classified Uncertain significance in COX10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). AlphaMissense: likely pathogenic (0.9926); Ultra-rare (popmax 0.0122%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COX10 p.Ser200Tyr (c.599C>A)?

COX10 p.Ser200Tyr (c.599C>A) is associated with Inborn genetic diseases, mitochondrial complex IV deficiency, nuclear type 3 (ClinVar).

How common is COX10 p.Ser200Tyr (c.599C>A) in the general population?

COX10 p.Ser200Tyr (c.599C>A) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about COX10 p.Ser200Tyr (c.599C>A)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

COX10 p.Ser200Tyr

c.599C>A · rs752287000 · VCV2509214

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic · top 5% in COX10
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -19.27	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 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.97 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0122% European (non-Finnish) · 144/1,179,712 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00995%

Overall 0.00917% 148/1,613,550 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,192
Remaining individualsnot grpmax-eligible	0.0032%	31,227
African / African-American	0.00267%	37,438

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.Ser200Tyr
Coding: c.599C>A
MANE Select: NM_001303
dbSNP: rs752287000
Type: single nucleotide variant
Location: chr17:14102217 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: mitochondrial complex IV deficiency, nuclear type 3

Similar variants

COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same condition
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.Ala175Ser Uncertain significance ★★ ⚠ same condition
COX10 p.Ala175Val 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-ser200tyr (accessed [today's date]).

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