Is COL11A2 p.Arg36Trp (c.106C>T) pathogenic?

COL11A2 p.Arg36Trp (c.106C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.1956); Ultra-rare (popmax 0.0557%, eas).

How common is COL11A2 p.Arg36Trp (c.106C>T) in the general population?

COL11A2 p.Arg36Trp (c.106C>T) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

What do computational predictors say about COL11A2 p.Arg36Trp (c.106C>T)?

AlphaMissense predicts likely benign (score 0.1956) — an in-silico prediction, not a clinical call.

COL11A2 p.Arg36Trp

c.106C>T · rs118097056 · VCV667101

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1956 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1956	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -11.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.4, phastCons 0.53
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	23.1	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 0.0557% East Asian · 25/44,884 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00298% 48/1,613,064 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,795
South Asian	0.00549%	18,216
African / African-American	0.004%	25,007
Admixed American	0.00333%	30,015
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.00102%	98,335

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.Arg36Trp
Coding: c.106C>T
MANE Select: NM_080680
dbSNP: rs118097056
Type: single nucleotide variant
Location: chr6:33189446 (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

Similar variants

COL11A2 p.Arg36Gln Uncertain significance ★★ ⚠ same residue
COL11A2 p.Arg36Gly Uncertain significance ★ ⚠ same residue
COL11A2 p.Arg36Leu Uncertain significance ★ ⚠ same residue
COL11A2 c.1119+1G>A Likely pathogenic ★★ same type
COL11A2 c.1819-2A>G Likely pathogenic ★★ same type
COL11A2 c.3852+1G>T Likely pathogenic ★★ same type
COL11A2 c.4392+1G>A Pathogenic ★★ same type
COL11A2 c.607-2A>T Likely pathogenic ★★ same type

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-arg36trp (accessed [today's date]).

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