Is COL11A2 p.Pro1503Ser (c.4507C>T) pathogenic?

COL11A2 p.Pro1503Ser (c.4507C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-06). AlphaMissense: ambiguous (0.458); Very rare (popmax 0.00186%, nfe).

How common is COL11A2 p.Pro1503Ser (c.4507C>T) in the general population?

COL11A2 p.Pro1503Ser (c.4507C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about COL11A2 p.Pro1503Ser (c.4507C>T)?

AlphaMissense predicts ambiguous (score 0.458) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro1503Ser

c.4507C>T · rs137923568 · VCV1355663

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.458 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Computational evidence

Protein change
AlphaMissense	0.458	ambiguous
REVEL	0.633	indeterminate
SaProt	LLR -6.29	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	23.9	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 0.00186% European (non-Finnish) · 22/1,180,038 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,613,358 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: COL11A2
Protein: p.Pro1503Ser
Coding: c.4507C>T
MANE Select: NM_080680
dbSNP: rs137923568
Type: single nucleotide variant
Location: chr6:33165792 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1503: the 'disordered' region

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

Similar variants

COL11A2 p.Pro1503= Likely benign ★ same residue
COL11A2 c.1119+1G>A Likely pathogenic ★★ same type
COL11A2 c.1819-2A>G Likely pathogenic ★★ same type
COL11A2 c.3852+1G>T Likely pathogenic ★★ same type
COL11A2 c.4392+1G>A Pathogenic ★★ same type
COL11A2 c.607-2A>T Likely pathogenic ★★ same type
COL11A2 c.876+1G>A Likely pathogenic ★★ same type
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ 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/col11a2-p-pro1503ser (accessed [today's date]).

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