Is COL11A2 p.Pro236Ser (c.706C>T) pathogenic?

COL11A2 p.Pro236Ser (c.706C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0736); Rare (popmax 0.111%, nfe); Associated with connective tissue disorder.

What condition is associated with COL11A2 p.Pro236Ser (c.706C>T)?

COL11A2 p.Pro236Ser (c.706C>T) is associated with connective tissue disorder (ClinVar).

How common is COL11A2 p.Pro236Ser (c.706C>T) in the general population?

COL11A2 p.Pro236Ser (c.706C>T) is rare (popmax 0.111%, nfe) (gnomAD).

What do computational predictors say about COL11A2 p.Pro236Ser (c.706C>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro236Ser

c.706C>T · rs35116188 · VCV388231

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

connective tissue disorder

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -6.83	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 4.8	GERP -2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	18.65	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 0.111% European (non-Finnish) · 1,312/1,180,016 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0841% 1,357/1,613,940 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.111%	899
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.0254%	3,939
Admixed American	0.00167%	59,998
Finnishnot grpmax-eligible	0.00156%	64,038

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.Pro236Ser
Coding: c.706C>T
MANE Select: NM_080680
dbSNP: rs35116188
Type: single nucleotide variant
Location: chr6:33186719 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 236: the 'nonhelical region' region; the 'disordered' region; a UniProt-annotated variant site (in)

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.Pro236= Likely benign ★ same residue
COL11A2 p.Arg876Met Uncertain significance ★★ ⚠ same condition
COL11A2 p.Pro524Ser 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

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-pro236ser (accessed [today's date]).

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