Is COL11A1 p.Pro576Arg (c.1727C>G) pathogenic?

COL11A1 p.Pro576Arg (c.1727C>G) is classified Uncertain significance in COL11A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.2194); Very rare (popmax 6.86e-05%); Associated with Inborn genetic diseases.

What condition is associated with COL11A1 p.Pro576Arg (c.1727C>G)?

COL11A1 p.Pro576Arg (c.1727C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COL11A1 p.Pro576Arg (c.1727C>G) in the general population?

COL11A1 p.Pro576Arg (c.1727C>G) is very rare (popmax 6.86e-05%) (gnomAD).

What do computational predictors say about COL11A1 p.Pro576Arg (c.1727C>G)?

AlphaMissense predicts likely benign (score 0.2194) — an in-silico prediction, not a clinical call.

COL11A1 p.Pro576Arg

c.1727C>G · rs2525408720 · VCV1987982

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2194 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.86e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2194	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -7.08	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 9.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 230 kb · p 0.038 · regional, not allelic
Overall
CADD	24.0	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 6.86e-05%

Overall 6.86e-05% 1/1,456,932 alleles · very rare

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: COL11A1
Protein: p.Pro576Arg
Coding: c.1727C>G
MANE Select: NM_001854
dbSNP: rs2525408720
Type: single nucleotide variant
Location: chr1:103006272 (GRCh38)
Gene constraint: LOEUF 0.349 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.06
Residue 576: the 'disordered' region; the 'triple-helical region' region; the collagen-like 2 domain

Full COL11A1 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

COL11A1 c.1629+1G>A Likely pathogenic ★★ same condition
COL11A1 p.Ala1002Val Uncertain significance ★★ ⚠ same condition
COL11A1 p.Ala1160Asp Uncertain significance ★★ ⚠ same condition
COL11A1 p.Ala1383Val Uncertain significance ★★ ⚠ same condition
COL11A1 p.Ala168Thr Uncertain significance ★★ ⚠ same condition
COL11A1 p.Ala73Val Uncertain significance ★★ ⚠ same condition
COL11A1 p.Arg1173Gly Uncertain significance ★★ ⚠ same condition
COL11A1 p.Arg564Gly 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/col11a1-p-pro576arg (accessed [today's date]).

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