Is COL6A1 p.Pro495Ser (c.1483C>T) pathogenic?

COL6A1 p.Pro495Ser (c.1483C>T) is classified Likely pathogenic in COL6A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-08). AlphaMissense: likely benign (0.0852); Absent from gnomAD v4.1; Associated with Ullrich congenital muscular dystrophy 1A.

What condition is associated with COL6A1 p.Pro495Ser (c.1483C>T)?

COL6A1 p.Pro495Ser (c.1483C>T) is associated with Ullrich congenital muscular dystrophy 1A (ClinVar).

How common is COL6A1 p.Pro495Ser (c.1483C>T) in the general population?

COL6A1 p.Pro495Ser (c.1483C>T) 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 COL6A1 p.Pro495Ser (c.1483C>T)?

AlphaMissense predicts likely benign (score 0.0852) — an in-silico prediction, not a clinical call.

COL6A1 p.Pro495Ser

c.1483C>T · rs1569518677 · VCV617567

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0852 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,222)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Ullrich congenital muscular dystrophy 1A

Computational evidence

Protein change
AlphaMissense	0.0852	likely benign ⚠ discordant with ClinVar
REVEL	0.294	indeterminate
SaProt	LLR -8.41	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 7.4	GERP 0.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 14 kb · p 0.038 · regional, not allelic
Overall
CADD	19.31	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

No allele count reported in gnomAD v4.1 (AN 1,595,222). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COL6A1
Protein: p.Pro495Ser
Coding: c.1483C>T
MANE Select: NM_001848
dbSNP: rs1569518677
Type: single nucleotide variant
Location: chr21:45997721 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.28 · 1 PDB
Residue 495: the 'disordered' region; the 'triple-helical region' region

Full COL6A1 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

COL6A1 p.Pro495= Likely benign ★ same residue
COL6A1 c.1575+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.428+1G>A Pathogenic ★★ same condition
COL6A1 c.805-2A>C Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.904-39A>G Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.930+189C>T Pathogenic/Likely pathogenic ★★ same condition
COL6A1 c.957+1G>A Pathogenic ★★ same condition
COL6A1 p.Gly281Arg 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/col6a1-p-pro495ser (accessed [today's date]).

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