Is COL11A2 p.Arg849Gln (c.2546G>A) pathogenic?

COL11A2 p.Arg849Gln (c.2546G>A) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-25). AlphaMissense: ambiguous (0.3785); Ultra-rare (popmax 0.0164%, mid).

How common is COL11A2 p.Arg849Gln (c.2546G>A) in the general population?

COL11A2 p.Arg849Gln (c.2546G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about COL11A2 p.Arg849Gln (c.2546G>A)?

AlphaMissense predicts ambiguous (score 0.3785) — an in-silico prediction, not a clinical call.

COL11A2 p.Arg849Gln

c.2546G>A · rs761524468 · VCV1060895

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.3785	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -7.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	26.2	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0018% 29/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00401%	24,957
European (non-Finnish)	0.00186%	53,635

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.Arg849Gln
Coding: c.2546G>A
MANE Select: NM_080680
dbSNP: rs761524468
Type: single nucleotide variant
Location: chr6:33173910 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 849: the 'disordered' region; the 'triple-helical region' region; the collagen-like 4 domain

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

Similar variants

COL11A2 p.Arg849Trp Likely benign ★ 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
COL11A2 c.876+1G>A Likely pathogenic ★★ same type
COL11A2 p.Arg1020Ter Pathogenic/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-arg849gln (accessed [today's date]).

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