Is COX11 p.Pro271Leu (c.812C>T) pathogenic?

COX11 p.Pro271Leu (c.812C>T) is classified Uncertain significance in COX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.1753); Very rare (popmax 0.00167%, amr).

How common is COX11 p.Pro271Leu (c.812C>T) in the general population?

COX11 p.Pro271Leu (c.812C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COX11 p.Pro271Leu (c.812C>T)?

AlphaMissense predicts likely benign (score 0.1753) — an in-silico prediction, not a clinical call.

COX11 p.Pro271Leu

c.812C>T · rs2077151925 · VCV2518343

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1753 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1753	likely benign
REVEL	0.389	indeterminate
SaProt	LLR -13.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 2.3, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 5,667 bp · p 0.00018 · 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 0.00167% Admixed American · 1/59,858 alleles

Overall 6.21e-05% 1/1,611,308 alleles · very rare exomes 0/1,459,286 · genomes 1/152,022 · 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.Pro271Leu
Coding: c.812C>T
MANE Select: NM_004375
dbSNP: rs2077151925
Type: single nucleotide variant
Location: chr17:54962752 (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-pro271leu (accessed [today's date]).

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