Is COX10 p.Ser103Ala (c.307T>G) pathogenic?

COX10 p.Ser103Ala (c.307T>G) is classified Uncertain significance in COX10 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-17). AlphaMissense: likely benign (0.0647); Ultra-rare (popmax 0.0461%, sas); Associated with mitochondrial complex IV deficiency, nuclear type 3.

What condition is associated with COX10 p.Ser103Ala (c.307T>G)?

COX10 p.Ser103Ala (c.307T>G) is associated with mitochondrial complex IV deficiency, nuclear type 3 (ClinVar).

How common is COX10 p.Ser103Ala (c.307T>G) in the general population?

COX10 p.Ser103Ala (c.307T>G) is ultra-rare (popmax 0.0461%, sas) (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.Ser103Ala (c.307T>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

COX10 p.Ser103Ala

c.307T>G · rs200480915 · VCV498097

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mitochondrial complex IV deficiency, nuclear type 3

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -2.9
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.97 · regional, not allelic
Overall
CADD	6.925	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0461% South Asian · 42/91,076 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00273% 44/1,614,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,168
Remaining individualsnot grpmax-eligible	0.0032%	31,251

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.Ser103Ala
Coding: c.307T>G
MANE Select: NM_001303
dbSNP: rs200480915
Type: single nucleotide variant
Location: chr17:14076864 (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 3 — 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.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.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-ser103ala (accessed [today's date]).

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