Is COL11A2 p.Pro1007Leu (c.3020C>T) pathogenic?

COL11A2 p.Pro1007Leu (c.3020C>T) is classified Conflicting classifications of pathogenicity in COL11A2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1963); Very rare (popmax 0.00237%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COL11A2 p.Pro1007Leu (c.3020C>T)?

COL11A2 p.Pro1007Leu (c.3020C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COL11A2 p.Pro1007Leu (c.3020C>T) in the general population?

COL11A2 p.Pro1007Leu (c.3020C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about COL11A2 p.Pro1007Leu (c.3020C>T)?

AlphaMissense predicts likely benign (score 0.1963) — an in-silico prediction, not a clinical call.

COL11A2 p.Pro1007Leu

c.3020C>T · rs771092817 · VCV1687700

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1963	likely benign
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -8.33	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.23	acceptor loss, 31 bp away · masked 0 · deltas
Pangolin	Δ0.28	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 3e-20 · regional, not allelic
Overall
CADD	31.0	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 0.00237% European (non-Finnish) · 28/1,179,938 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00223% 36/1,612,634 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00636%	15,728
Remaining individualsnot grpmax-eligible	0.0032%	31,236
European (non-Finnish)grpmax	0.00237%	42,141
Admixed American	0.00167%	59,988
South Asian	0.0011%	91,054

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1007Leu
Coding: c.3020C>T
MANE Select: NM_080680
dbSNP: rs771092817
Type: single nucleotide variant
Location: chr6:33172072 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.18
Residue 1007: the 'disordered' region; the 'triple-helical region' region

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.Pro1007= Likely benign ★★ same residue
COL11A2 p.Pro1007Ser Uncertain significance ★ ⚠ 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
COL11A2 p.Arg36Gln 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-pro1007leu (accessed [today's date]).

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