Is COX10 p.Cys243Ser (c.727T>A) pathogenic?

COX10 p.Cys243Ser (c.727T>A) is classified Uncertain significance in COX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: ambiguous (0.3836); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with COX10 p.Cys243Ser (c.727T>A)?

COX10 p.Cys243Ser (c.727T>A) is associated with Inborn genetic diseases (ClinVar).

How common is COX10 p.Cys243Ser (c.727T>A) in the general population?

COX10 p.Cys243Ser (c.727T>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about COX10 p.Cys243Ser (c.727T>A)?

AlphaMissense predicts ambiguous (score 0.3836) — an in-silico prediction, not a clinical call.

COX10 p.Cys243Ser

c.727T>A · rs756279622 · VCV2519922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3836	ambiguous
REVEL	0.656	pathogenic-leaning
SaProt	LLR -10.30	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.37	gain · loss 0.23 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	24.1	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 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00041% 6/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
European (non-Finnish)	0.000254%	393,349

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.Cys243Ser
Coding: c.727T>A
MANE Select: NM_001303
dbSNP: rs756279622
Type: single nucleotide variant
Location: chr17:14192020 (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

Similar variants

COX10 p.Ala175Ser Uncertain significance ★★ ⚠ same condition
COX10 p.Ala303Asp Uncertain significance ★★ ⚠ same condition
COX10 p.Arg334His Uncertain significance ★★ ⚠ same condition
COX10 p.Arg398Cys Uncertain significance ★★ ⚠ same condition
COX10 p.Asp308Asn Uncertain significance ★★ ⚠ same condition
COX10 p.Cys243del Uncertain significance ★★ same residue
COX10 p.Glu25Gly Uncertain significance ★★ ⚠ same condition
COX10 p.Gly434Arg 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-cys243ser (accessed [today's date]).

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