Is COL12A1 p.Pro384Ser (c.1150C>T) pathogenic?

COL12A1 p.Pro384Ser (c.1150C>T) is classified Conflicting classifications of pathogenicity in COL12A1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.139); Ultra-rare (popmax 0.0209%, sas); Associated with Ullrich congenital muscular dystrophy 2.

What condition is associated with COL12A1 p.Pro384Ser (c.1150C>T)?

COL12A1 p.Pro384Ser (c.1150C>T) is associated with Ullrich congenital muscular dystrophy 2, Bethlem myopathy 2 (ClinVar).

How common is COL12A1 p.Pro384Ser (c.1150C>T) in the general population?

COL12A1 p.Pro384Ser (c.1150C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

How is Ullrich congenital muscular dystrophy inherited?

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

What do computational predictors say about COL12A1 p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

COL12A1 p.Pro384Ser

c.1150C>T · rs370952607 · VCV935074

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Ullrich congenital muscular dystrophy 2

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.187	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	25.0	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 0.0209% South Asian · 19/91,094 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00304% 49/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00246%	40,691

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.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_004370
dbSNP: rs370952607
Type: single nucleotide variant
Location: chr6:75183992 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Residue 384: the fibronectin type-iii 2 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.Pro384= Likely benign ★★ same residue
COL12A1 p.Pro384Leu 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

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-pro384ser (accessed [today's date]).

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