Is COL11A2 p.Arg36Gln (c.107G>A) pathogenic?

COL11A2 p.Arg36Gln (c.107G>A) is classified Uncertain significance in COL11A2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0874); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with COL11A2 p.Arg36Gln (c.107G>A)?

COL11A2 p.Arg36Gln (c.107G>A) is associated with Inborn genetic diseases (ClinVar).

How common is COL11A2 p.Arg36Gln (c.107G>A) in the general population?

COL11A2 p.Arg36Gln (c.107G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COL11A2 p.Arg36Gln (c.107G>A)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

COL11A2 p.Arg36Gln

c.107G>A · rs757584689 · VCV1386768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.26	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 -5.3	GERP -3.4
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	9.897	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00093% 15/1,612,932 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00159%	62,940
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000932%	107,275

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.Arg36Gln
Coding: c.107G>A
MANE Select: NM_080680
dbSNP: rs757584689
Type: single nucleotide variant
Location: chr6:33189445 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL11A2 p.Arg36Gly Uncertain significance ★ ⚠ same residue
COL11A2 p.Arg36Leu Uncertain significance ★ ⚠ same residue
COL11A2 p.Arg36Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
COL11A2 p.Ala216Glu Uncertain significance ★★ ⚠ same condition
COL11A2 p.Ala66Pro Uncertain significance ★★ ⚠ same condition
COL11A2 p.Ala827Gly Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg1596Gln Uncertain significance ★★ ⚠ same condition
COL11A2 p.Arg1667Ser Uncertain significance ★★ ⚠ 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-arg36gln (accessed [today's date]).

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