Is COL6A2 p.Pro341Thr (c.1021C>A) pathogenic?

COL6A2 p.Pro341Thr (c.1021C>A) is classified Likely pathogenic in COL6A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: likely benign (0.1148); Absent from gnomAD v4.1; Associated with Ullrich congenital muscular dystrophy 1A.

What condition is associated with COL6A2 p.Pro341Thr (c.1021C>A)?

COL6A2 p.Pro341Thr (c.1021C>A) is associated with Ullrich congenital muscular dystrophy 1A (ClinVar).

How common is COL6A2 p.Pro341Thr (c.1021C>A) in the general population?

COL6A2 p.Pro341Thr (c.1021C>A) is absent from gnomAD v4.1 (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 COL6A2 p.Pro341Thr (c.1021C>A)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

COL6A2 p.Pro341Thr

c.1021C>A · rs2078489585 · VCV2572201

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Ullrich congenital muscular dystrophy 1A

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign ⚠ discordant with ClinVar
REVEL	0.431	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 16 kb · p 1.4e-07 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COL6A2
Protein: p.Pro341Thr
Coding: c.1021C>A
MANE Select: NM_001849
dbSNP: rs2078489585
Type: single nucleotide variant
Location: chr21:46117421 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 341: the 'triple-helical region' region; the 'disordered' region

Full COL6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ullrich congenital muscular dystrophy 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ullrich congenital muscular dystrophy (Orphanet):

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

Similar variants

COL6A2 p.Pro341Leu Uncertain significance ★★ ⚠ same residue
COL6A2 p.Pro341Ser Uncertain significance ★★ ⚠ same residue
COL6A2 c.1970-9G>A Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.2422+1G>A Pathogenic ★★ same condition
COL6A2 c.736-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.900+2T>G Pathogenic/Likely pathogenic ★★ same condition
COL6A2 p.Arg539Ter Pathogenic/Likely pathogenic ★★ same condition
COL6A2 p.Arg876His 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/col6a2-p-pro341thr (accessed [today's date]).

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