Is COX11 p.Pro241Ala (c.721C>G) pathogenic?

COX11 p.Pro241Ala (c.721C>G) is classified Uncertain significance in COX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: ambiguous (0.4545); Very rare (popmax 0.00119%, nfe).

How common is COX11 p.Pro241Ala (c.721C>G) in the general population?

COX11 p.Pro241Ala (c.721C>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about COX11 p.Pro241Ala (c.721C>G)?

AlphaMissense predicts ambiguous (score 0.4545) — an in-silico prediction, not a clinical call.

COX11 p.Pro241Ala

c.721C>G · VCV4655948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4545	ambiguous
REVEL	0.696	pathogenic-leaning
SaProt	LLR -11.95	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,667 bp · p 0.00018 · regional, not allelic
Overall
CADD	27.6	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 0.00119% European (non-Finnish) · 14/1,179,326 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000868% 14/1,612,964 alleles · very rare exomes 11/1,460,930 · genomes 3/152,034 · joint denominator

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.Pro241Ala
Coding: c.721C>G
MANE Select: NM_004375
Type: single nucleotide variant
Location: chr17:54962843 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 74.29

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.Arg64Trp 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

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-pro241ala (accessed [today's date]).

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