Is COL11A2 p.Arg720Pro (c.2159G>C) pathogenic?

COL11A2 p.Arg720Pro (c.2159G>C) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.9221); Very rare (popmax 0.00223%, eas).

How common is COL11A2 p.Arg720Pro (c.2159G>C) in the general population?

COL11A2 p.Arg720Pro (c.2159G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COL11A2 p.Arg720Pro (c.2159G>C)?

AlphaMissense predicts likely pathogenic (score 0.9221) — an in-silico prediction, not a clinical call.

COL11A2 p.Arg720Pro

c.2159G>C · rs756050324 · VCV2988006

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9221 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9221	likely pathogenic
REVEL	0.582	indeterminate
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	28.2	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 0.00223% East Asian · 1/44,860 alleles

Overall 6.85e-05% 1/1,460,300 alleles · very rare

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.Arg720Pro
Coding: c.2159G>C
MANE Select: NM_080680
dbSNP: rs756050324
Type: single nucleotide variant
Location: chr6:33176443 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 720: the 'disordered' region; the 'triple-helical region' region

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

Similar variants

COL11A2 p.Arg720Ter Pathogenic/Likely pathogenic ★★ same residue
COL11A2 p.Arg720Gln 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

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-arg720pro (accessed [today's date]).

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