Is COL12A1 p.Ser2001= (c.6003C>T) pathogenic?

COL12A1 p.Ser2001= (c.6003C>T) is classified Likely benign in COL12A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00144%, nfe); Associated with Ullrich congenital muscular dystrophy 2.

What condition is associated with COL12A1 p.Ser2001= (c.6003C>T)?

COL12A1 p.Ser2001= (c.6003C>T) is associated with Ullrich congenital muscular dystrophy 2, Bethlem myopathy 2 (ClinVar).

How common is COL12A1 p.Ser2001= (c.6003C>T) in the general population?

COL12A1 p.Ser2001= (c.6003C>T) is very rare (popmax 0.00144%, nfe) (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.Ser2001=

c.6003C>T · rs762626921 · VCV711362

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

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 -0.89	GERP -3.5
Overall
CADD	5.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,006 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00118% 19/1,613,966 alleles · very rare exomes 18/1,461,848 · genomes 1/152,118 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,011
European (non-Finnish)grpmax	0.00144%	69,412

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: COL12A1
Protein: p.Ser2001=
Coding: c.6003C>T
MANE Select: NM_004370
dbSNP: rs762626921
Type: single nucleotide variant
Location: chr6:75130916 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Residue 2001: the fibronectin type-iii 15 domain

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.Ser2001Cys 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
COL12A1 p.Arg1299Ter Pathogenic/Likely pathogenic ★★ same condition
COL12A1 p.Arg1301Ter Pathogenic/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-ser2001 (accessed [today's date]).

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