Is COX10 p.Arg409Trp (c.1225C>T) pathogenic?

COX10 p.Arg409Trp (c.1225C>T) is classified Conflicting classifications of pathogenicity in COX10 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-20). AlphaMissense: likely pathogenic (0.6992); Very rare (popmax 0.00551%, nfe).

How common is COX10 p.Arg409Trp (c.1225C>T) in the general population?

COX10 p.Arg409Trp (c.1225C>T) is very rare (popmax 0.00551%, nfe) (gnomAD).

What do computational predictors say about COX10 p.Arg409Trp (c.1225C>T)?

AlphaMissense predicts likely pathogenic (score 0.6992) — an in-silico prediction, not a clinical call.

COX10 p.Arg409Trp

c.1225C>T · rs368918847 · VCV418144

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00551%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6992	likely pathogenic
REVEL	0.634	indeterminate
SaProt	LLR -12.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -2.8
Regional constraint	o/e 0.89	unconstrained · MANE · 372 bp · p 0.13 · regional, not allelic
Overall
CADD	19.81	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 0.00551% European (non-Finnish) · 65/1,179,936 alleles

Filtering AF 0.00443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00403%

Overall 0.00428% 69/1,613,696 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00551%	18,153
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00133%	74,924
South Asian	0.0011%	91,090

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.Arg409Trp
Coding: c.1225C>T
MANE Select: NM_001303
dbSNP: rs368918847
Type: single nucleotide variant
Location: chr17:14207106 (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

Similar variants

COX10 p.Asp336Val Pathogenic/Likely pathogenic ★★ same type
COX10 p.Gln230Ter Likely pathogenic ★★ same type
COX10 p.Pro225Leu Likely pathogenic ★★ same type
COX10 c.-89G>C Uncertain significance ★★ same type
COX10 c.-89G>T Uncertain significance ★★ same type
COX10 p.Ala174Thr Uncertain significance ★★ ⚠ same type
COX10 p.Ala175Ser Uncertain significance ★★ ⚠ same type
COX10 p.Ala175Val Uncertain significance ★★ ⚠ same type

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-arg409trp (accessed [today's date]).

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