Is COL11A2 p.Pro1109Ser (c.3325C>T) pathogenic?

COL11A2 p.Pro1109Ser (c.3325C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-10). AlphaMissense: likely benign (0.1443); Very rare (popmax 0.00852%, nfe).

How common is COL11A2 p.Pro1109Ser (c.3325C>T) in the general population?

COL11A2 p.Pro1109Ser (c.3325C>T) is very rare (popmax 0.00852%, nfe) (gnomAD).

What do computational predictors say about COL11A2 p.Pro1109Ser (c.3325C>T)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro1109Ser

c.3325C>T · rs761687232 · VCV286761

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00852%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.758	pathogenic-leaning
SaProt	—	withheld · numbering disagrees past residue 894 · why
⇒ REVEL calls this damaging; AlphaMissense does not; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00852% European (non-Finnish) · 100/1,174,168 alleles

Filtering AF 0.00711% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00663%

Overall 0.00643% 103/1,603,034 alleles · very rare exomes 98/1,450,936 · genomes 5/152,098 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00852%	11,742
Admixed American	0.00174%	57,536
Remaining individualsnot grpmax-eligible	0.00161%	62,120
African / African-American	0.00134%	74,736

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.Pro1109Ser
Coding: c.3325C>T
MANE Select: NM_080680
dbSNP: rs761687232
Type: single nucleotide variant
Location: chr6:33171155 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1109: the 'disordered' region; the 'triple-helical region' region; the collagen-like 6 domain

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

Similar variants

COL11A2 p.Pro1109His Conflicting classifications of pathogenicity ★ ⚠ same residue
COL11A2 p.Pro1109= 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-pro1109ser (accessed [today's date]).

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