Is COL11A2 p.Pro809Ala (c.2425C>G) pathogenic?

COL11A2 p.Pro809Ala (c.2425C>G) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-17). AlphaMissense: likely benign (0.0615); Ultra-rare (popmax 0.0165%, mid); Associated with COL11A2-related disorder.

What condition is associated with COL11A2 p.Pro809Ala (c.2425C>G)?

COL11A2 p.Pro809Ala (c.2425C>G) is associated with COL11A2-related disorder (ClinVar).

How common is COL11A2 p.Pro809Ala (c.2425C>G) in the general population?

COL11A2 p.Pro809Ala (c.2425C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about COL11A2 p.Pro809Ala (c.2425C>G)?

AlphaMissense predicts likely benign (score 0.0615) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro809Ala

c.2425C>G · rs1483323590 · VCV1365894

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0615 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

COL11A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0615	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -7.61	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	24.4	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 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,612,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)	0.000254%	393,311

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.Pro809Ala
Coding: c.2425C>G
MANE Select: NM_080680
dbSNP: rs1483323590
Type: single nucleotide variant
Location: chr6:33174532 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 809: the 'disordered' region; the 'triple-helical region' region; the collagen-like 4 domain

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

Disease context

COL11A2-related disorder

Similar variants

COL11A2 p.Pro809Leu Uncertain significance ★★ ⚠ same residue
COL11A2 c.1119+1G>A Likely pathogenic ★★ same condition
COL11A2 c.4392+1G>A Pathogenic ★★ same condition
COL11A2 c.607-2A>T Likely pathogenic ★★ same condition
COL11A2 p.Arg1034Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
COL11A2 p.Arg1061Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1320Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1379Ter Pathogenic/Likely pathogenic ★★ 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-pro809ala (accessed [today's date]).

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