Is COL11A2 p.Pro524Ser (c.1570C>T) pathogenic?

COL11A2 p.Pro524Ser (c.1570C>T) is classified Uncertain significance in COL11A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-20). AlphaMissense: likely benign (0.0783); Absent from gnomAD v4.1; Associated with connective tissue disorder.

What condition is associated with COL11A2 p.Pro524Ser (c.1570C>T)?

COL11A2 p.Pro524Ser (c.1570C>T) is associated with connective tissue disorder (ClinVar).

How common is COL11A2 p.Pro524Ser (c.1570C>T) in the general population?

COL11A2 p.Pro524Ser (c.1570C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COL11A2 p.Pro524Ser (c.1570C>T)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro524Ser

c.1570C>T · rs2150579159 · VCV1702446

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.462	indeterminate
SaProt	LLR -8.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL11A2
Protein: p.Pro524Ser
Coding: c.1570C>T
MANE Select: NM_080680
dbSNP: rs2150579159
Type: single nucleotide variant
Location: chr6:33179114 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 524: the 'disordered' region; the 'triple-helical region' region; the collagen-like 2 domain

Full COL11A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL11A2 p.Arg876Met Uncertain significance ★★ ⚠ same condition
COL11A2 c.1284+8G>A Likely benign ★★ same condition
COL11A2 c.1446+19C>T Likely benign ★★ same condition
COL11A2 c.1612-16T>A Likely benign ★★ same condition
COL11A2 c.3475-19G>A Likely benign ★★ same condition
COL11A2 c.3583-5T>C Benign/Likely benign ★★ same condition
COL11A2 c.4750+19G>T Likely benign ★★ same condition
COL11A2 c.5071-5T>G Benign/Likely benign ★★ 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/col11a2-p-pro524ser (accessed [today's date]).

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