Is COL6A3 p.Phe375= (c.1125C>T) pathogenic?

COL6A3 p.Phe375= (c.1125C>T) is classified Uncertain significance in COL6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 6.2e-05%); Associated with collagen 6-related myopathy.

What condition is associated with COL6A3 p.Phe375= (c.1125C>T)?

COL6A3 p.Phe375= (c.1125C>T) is associated with collagen 6-related myopathy (ClinVar).

How common is COL6A3 p.Phe375= (c.1125C>T) in the general population?

COL6A3 p.Phe375= (c.1125C>T) is very rare (popmax 6.2e-05%) (gnomAD).

COL6A3 p.Phe375=

c.1125C>T · rs2078184502 · VCV896590

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

collagen 6-related myopathy

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 3.3	GERP 0.57, phastCons 1
Overall
CADD	9.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 1/1,461,724 · genomes 0/152,288 · 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: COL6A3
Protein: p.Phe375=
Coding: c.1125C>T
MANE Select: NM_004369
dbSNP: rs2078184502
Type: single nucleotide variant
Location: chr2:237387769 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 375: the 'nonhelical region' region; the vwfa 2 domain

Full COL6A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

collagen 6-related myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A3 p.Ala1370Ser Uncertain significance ★★ same condition
COL6A3 p.Ala163Val Uncertain significance ★★ same condition
COL6A3 p.Arg1975Leu Uncertain significance ★★ ⚠ same condition
COL6A3 p.Arg1998Gln Uncertain significance ★★ same condition
COL6A3 p.Arg935Trp Uncertain significance ★★ same condition
COL6A3 p.Asp1278Asn Uncertain significance ★★ ⚠ 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/col6a3-p-phe375 (accessed [today's date]).

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