Is COL6A2 p.Arg202Trp (c.604C>T) pathogenic?

COL6A2 p.Arg202Trp (c.604C>T) is classified Uncertain significance in COL6A2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1576); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with COL6A2 p.Arg202Trp (c.604C>T)?

COL6A2 p.Arg202Trp (c.604C>T) is associated with Inborn genetic diseases, Bethlem myopathy 1A (ClinVar).

How common is COL6A2 p.Arg202Trp (c.604C>T) in the general population?

COL6A2 p.Arg202Trp (c.604C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about COL6A2 p.Arg202Trp (c.604C>T)?

AlphaMissense predicts likely benign (score 0.1576) — an in-silico prediction, not a clinical call.

COL6A2 p.Arg202Trp

c.604C>T · rs924873209 · VCV1988483

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1576	likely benign
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -9.23	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.57, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 2,585 bp · p 0.043 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.0011% 16/1,458,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,448
South Asian	0.0011%	91,038
European (non-Finnish)	0.000932%	107,247

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: COL6A2
Protein: p.Arg202Trp
Coding: c.604C>T
MANE Select: NM_001849
dbSNP: rs924873209
Type: single nucleotide variant
Location: chr21:46112467 (GRCh38)
Gene constraint: LOEUF 0.895 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 1 PDB
Residue 202: the vwfa 1 domain; the 'nonhelical region' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bethlem myopathy 1A

Similar variants

COL6A2 p.Arg202Gln Uncertain significance ★ ⚠ same residue
COL6A2 c.1000-1G>T Pathogenic ★★ same condition
COL6A2 c.1000-2A>C Pathogenic ★★ same condition
COL6A2 c.1053+1G>A Pathogenic ★★ same condition
COL6A2 c.1053+1G>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1053+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.1054-2A>G Pathogenic/Likely pathogenic ★★ same condition
COL6A2 c.115+2T>C Pathogenic/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-arg202trp (accessed [today's date]).

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