Is COL12A1 p.Pro2802= (c.8406G>A) pathogenic?

COL12A1 p.Pro2802= (c.8406G>A) is classified Likely benign in COL12A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.0145%, amr); Associated with Ullrich congenital muscular dystrophy 2.

What condition is associated with COL12A1 p.Pro2802= (c.8406G>A)?

COL12A1 p.Pro2802= (c.8406G>A) is associated with Ullrich congenital muscular dystrophy 2, Bethlem myopathy 2 (ClinVar).

How common is COL12A1 p.Pro2802= (c.8406G>A) in the general population?

COL12A1 p.Pro2802= (c.8406G>A) is ultra-rare (popmax 0.0145%, amr) (gnomAD).

How is Ullrich congenital muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COL12A1 p.Pro2802=

c.8406G>A · rs761216954 · VCV950747

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, amr)

Conditions

Ullrich congenital muscular dystrophy 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.1
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0145% Admixed American · 7/48,392 alleles

Filtering AF 0.00669% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00475%

Overall 0.000909% 14/1,540,750 alleles · ultra-rare exomes 8/1,388,636 · genomes 6/152,114 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0145%	6,913
Remaining individualsnot grpmax-eligible	0.00509%	19,644
African / African-American	0.00141%	70,904
South Asian	0.00125%	79,816
European (non-Finnish)	0.000175%	572,833

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: COL12A1
Protein: p.Pro2802=
Coding: c.8406G>A
MANE Select: NM_004370
dbSNP: rs761216954
Type: single nucleotide variant
Location: chr6:75102606 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Residue 2802: the collagen-like 2 domain; the 'disordered' region; the 'triple-helical region (col2) with 1 imperfection' region

Full COL12A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ullrich congenital muscular dystrophy 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bethlem myopathy 2

For Ullrich congenital muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (United Kingdom)

Similar variants

COL12A1 p.Pro2802Leu Conflicting classifications of pathogenicity ★ same residue
COL12A1 p.Pro2802Thr Uncertain significance ★ same residue
COL12A1 p.Pro2802Arg Uncertain significance ★ ⚠ same residue
COL12A1 c.4418-1G>A Likely pathogenic ★★ same condition
COL12A1 c.4957+1G>A Likely pathogenic ★★ same condition
COL12A1 c.5230+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL12A1 c.5794+2T>A Pathogenic ★★ same condition
COL12A1 c.7519+1G>A Likely pathogenic ★★ 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/col12a1-p-pro2802 (accessed [today's date]).

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