Is COL11A2 p.Pro623= (c.1869C>G) pathogenic?

COL11A2 p.Pro623= (c.1869C>G) is classified Uncertain significance in COL11A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00034%, nfe); Associated with otospondylomegaepiphyseal dysplasia, autosomal dominant.

What condition is associated with COL11A2 p.Pro623= (c.1869C>G)?

COL11A2 p.Pro623= (c.1869C>G) is associated with otospondylomegaepiphyseal dysplasia, autosomal dominant, fibrochondrogenesis 2, otospondylomegaepiphyseal dysplasia, autosomal recessive (ClinVar).

How common is COL11A2 p.Pro623= (c.1869C>G) in the general population?

COL11A2 p.Pro623= (c.1869C>G) is very rare (popmax 0.00034%, nfe) (gnomAD).

COL11A2 p.Pro623=

Q: How is Autosomal recessive otospondylomegaepiphyseal dysplasia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1869C>G · rs1771179784 · VCV903890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Conditions

otospondylomegaepiphyseal dysplasia, autosomal dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.28	GERP -2.6, phastCons 0.016
Overall
CADD	7.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00034% European (non-Finnish) · 4/1,177,526 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000311% 5/1,609,056 alleles · very rare exomes 5/1,456,956 · genomes 0/152,100 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,312
European (non-Finnish)grpmax	0.00034%	294,382

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro623=
Coding: c.1869C>G
MANE Select: NM_080680
dbSNP: rs1771179784
Type: single nucleotide variant
Location: chr6:33178135 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 623: the 'disordered' region; the 'triple-helical region' region

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

Disease context

otospondylomegaepiphyseal dysplasia, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fibrochondrogenesis 2 otospondylomegaepiphyseal dysplasia, autosomal recessive

For Autosomal recessive otospondylomegaepiphyseal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

COL11A2 p.Pro623Ser Uncertain significance ★ ⚠ same residue
COL11A2 p.Pro623Thr Uncertain significance ★ ⚠ same residue
COL11A2 c.4392+1G>A Pathogenic ★★ same condition
COL11A2 p.Arg1020Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1331Ter Pathogenic ★★ same condition
COL11A2 p.Arg1379Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg1600Ter Pathogenic/Likely pathogenic ★★ same condition
COL11A2 p.Arg379Ter 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-pro623 (accessed [today's date]).

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