Is COL12A1 p.Pro511Ser (c.1531C>T) pathogenic?

COL12A1 p.Pro511Ser (c.1531C>T) is classified Likely benign in COL12A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely pathogenic (0.7659); Very rare (popmax 0.00127%, nfe); Associated with Ullrich congenital muscular dystrophy 2.

What condition is associated with COL12A1 p.Pro511Ser (c.1531C>T)?

COL12A1 p.Pro511Ser (c.1531C>T) is associated with Ullrich congenital muscular dystrophy 2, Bethlem myopathy 2 (ClinVar).

How common is COL12A1 p.Pro511Ser (c.1531C>T) in the general population?

COL12A1 p.Pro511Ser (c.1531C>T) is very rare (popmax 0.00127%, 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.

What do computational predictors say about COL12A1 p.Pro511Ser (c.1531C>T)?

AlphaMissense predicts likely pathogenic (score 0.7659) — an in-silico prediction, not a clinical call.

COL12A1 p.Pro511Ser

c.1531C>T · rs751220055 · VCV2142823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Conditions

Ullrich congenital muscular dystrophy 2

Computational evidence

Protein change
AlphaMissense	0.7659	likely pathogenic
REVEL	0.597	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 81 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	27.9	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 0.00127% European (non-Finnish) · 15/1,180,040 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,014 alleles · very rare exomes 14/1,461,854 · genomes 1/152,160 · joint denominator

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.Pro511Ser
Coding: c.1531C>T
MANE Select: NM_004370
dbSNP: rs751220055
Type: single nucleotide variant
Location: chr6:75183410 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Residue 511: the vwfa 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 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
COL12A1 p.Arg1396Ter 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-pro511ser (accessed [today's date]).

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