Is COL11A2 p.Ile210Val (c.628A>G) pathogenic?

COL11A2 p.Ile210Val (c.628A>G) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-09). AlphaMissense: likely benign (0.1372); Very rare (popmax 0.00668%, afr); Associated with otospondylomegaepiphyseal dysplasia, autosomal dominant.

What condition is associated with COL11A2 p.Ile210Val (c.628A>G)?

COL11A2 p.Ile210Val (c.628A>G) is associated with otospondylomegaepiphyseal dysplasia, autosomal dominant (ClinVar).

How common is COL11A2 p.Ile210Val (c.628A>G) in the general population?

COL11A2 p.Ile210Val (c.628A>G) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about COL11A2 p.Ile210Val (c.628A>G)?

AlphaMissense predicts likely benign (score 0.1372) — an in-silico prediction, not a clinical call.

COL11A2 p.Ile210Val

Q: How is Autosomal recessive otospondylomegaepiphyseal dysplasia inherited?

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

c.628A>G · rs778295133 · VCV547921

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1372 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

otospondylomegaepiphyseal dysplasia, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.1372	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.11	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 0.39	GERP -0.53, phastCons 0.98
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	11.79	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 0.00668% African / African-American · 5/74,864 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00161% 26/1,613,926 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,973
European (non-Finnish)	0.00178%	56,191

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.Ile210Val
Coding: c.628A>G
MANE Select: NM_080680
dbSNP: rs778295133
Type: single nucleotide variant
Location: chr6:33186797 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 210: the laminin g-like domain

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

For Autosomal recessive otospondylomegaepiphyseal dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

COL11A2 p.Ile210Met Uncertain significance ★ ⚠ same residue
COL11A2 p.Ile210= Likely benign ★ 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-ile210val (accessed [today's date]).

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