Is COX10 p.Thr7Ser (c.20C>G) pathogenic?

COX10 p.Thr7Ser (c.20C>G) is classified Uncertain significance in COX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.0788); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with COX10 p.Thr7Ser (c.20C>G)?

COX10 p.Thr7Ser (c.20C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COX10 p.Thr7Ser (c.20C>G) in the general population?

COX10 p.Thr7Ser (c.20C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COX10 p.Thr7Ser (c.20C>G)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

COX10 p.Thr7Ser

c.20C>G · rs756920451 · VCV3076428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.14	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 3.8	GERP 1.2, phastCons 0.19
Regional constraint	o/e 1.00	unconstrained · MANE · 90 kb · p 0.97 · regional, not allelic
Overall
CADD	15.18	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00136% 22/1,614,016 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
European (non-Finnish)	0.00169%	59,001
South Asian	0.0011%	91,076

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.Thr7Ser
Coding: c.20C>G
MANE Select: NM_001303
dbSNP: rs756920451
Type: single nucleotide variant
Location: chr17:14069625 (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.Glu25Gly Uncertain significance ★★ ⚠ same condition
COX10 p.Gly434Arg Uncertain significance ★★ ⚠ same condition
COX10 p.Gly436Arg 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-thr7ser (accessed [today's date]).

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