Is COX11 p.Arg64Trp (c.190C>T) pathogenic?

COX11 p.Arg64Trp (c.190C>T) is classified Uncertain significance in COX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.0979); Ultra-rare (popmax 0.0133%, amr).

How common is COX11 p.Arg64Trp (c.190C>T) in the general population?

COX11 p.Arg64Trp (c.190C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about COX11 p.Arg64Trp (c.190C>T)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

COX11 p.Arg64Trp

c.190C>T · VCV4005962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -6.40	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 0.46	GERP -2.9
Regional constraint	o/e 1.23	unconstrained · MANE · 242 bp · p 0.02 · regional, not allelic
Overall
CADD	13.44	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 0.0133% Admixed American · 8/60,016 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000744% 12/1,613,422 alleles · ultra-rare exomes 12/1,461,308 · genomes 0/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0016%	62,496
Finnishnot grpmax-eligible	0.00158%	63,450
European (non-Finnish)	0.000169%	589,984

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: COX11
Protein: p.Arg64Trp
Coding: c.190C>T
MANE Select: NM_004375
Type: single nucleotide variant
Location: chr17:54968457 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.29
Residue 64: the 'disordered' region

Full COX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX11 p.Ala109Val Uncertain significance ★ ⚠ same type
COX11 p.Ala132Val Uncertain significance ★ ⚠ same type
COX11 p.Ala67Val Uncertain significance ★ ⚠ same type
COX11 p.Arg148Gln Uncertain significance ★ ⚠ same type
COX11 p.Asp253Val Uncertain significance ★ ⚠ same type
COX11 p.Cys11Tyr Uncertain significance ★ ⚠ same type
COX11 p.Cys121Tyr Uncertain significance ★ ⚠ same type
COX11 p.Gln91Pro 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/cox11-p-arg64trp (accessed [today's date]).

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