Is COL6A3 p.Phe597= (c.1791C>T) pathogenic?

COL6A3 p.Phe597= (c.1791C>T) is classified Benign/Likely benign in COL6A3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). Low-frequency (popmax 2.62%, afr); Associated with collagen 6-related myopathy.

What condition is associated with COL6A3 p.Phe597= (c.1791C>T)?

COL6A3 p.Phe597= (c.1791C>T) is associated with collagen 6-related myopathy, Bethlem myopathy 1A (ClinVar).

How common is COL6A3 p.Phe597= (c.1791C>T) in the general population?

COL6A3 p.Phe597= (c.1791C>T) is low-frequency (popmax 2.62%, afr) (gnomAD).

COL6A3 p.Phe597=

c.1791C>T · rs76576170 · VCV235508

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.62%, afr)

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 -2.4	GERP -3.4
Overall
CADD	0.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.62% African / African-American · 1,969/75,038 alleles

Filtering AF 2.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.49%

Overall 0.148% 2,383/1,614,192 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.62%	38
Middle Eastern	0.347%	289
Admixed American	0.242%	414
Remaining individualsnot grpmax-eligible	0.198%	504
European (non-Finnish)	0.00991%	10,086
South Asian	0.00659%	15,181
East Asian	0.00223%	44,880

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.Phe597=
Coding: c.1791C>T
MANE Select: NM_004369
dbSNP: rs76576170
Type: single nucleotide variant
Location: chr2:237381021 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 597: the 'nonhelical region' region; the vwfa 3 domain

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

Disease context

Also linked: Bethlem myopathy 1A

Similar variants

COL6A3 p.Phe597Leu Conflicting classifications of pathogenicity ★ same residue
COL6A3 c.5838+1G>T Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6156+1G>A Pathogenic ★★ same condition
COL6A3 c.6157-2A>C Pathogenic ★★ same condition
COL6A3 c.6210+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>A Pathogenic ★★ same condition
COL6A3 c.6282+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A3 c.6309+1G>A 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/col6a3-p-phe597 (accessed [today's date]).

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