Is COL7A1 p.Arg2685Pro (c.8054G>C) pathogenic?

COL7A1 p.Arg2685Pro (c.8054G>C) is classified Uncertain significance in COL7A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-28). AlphaMissense: likely pathogenic (0.6101); Very rare (popmax 0.00833%, amr); Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Arg2685Pro (c.8054G>C)?

COL7A1 p.Arg2685Pro (c.8054G>C) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Arg2685Pro (c.8054G>C) in the general population?

COL7A1 p.Arg2685Pro (c.8054G>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about COL7A1 p.Arg2685Pro (c.8054G>C)?

AlphaMissense predicts likely pathogenic (score 0.6101) — an in-silico prediction, not a clinical call.

COL7A1 p.Arg2685Pro

c.8054G>C · rs886058630 · VCV345800

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6101 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

epidermolysis bullosa dystrophica

Computational evidence

Protein change
AlphaMissense	0.6101	likely pathogenic
REVEL	0.529	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 22 kb · p 7.2e-17 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.00833% Admixed American · 5/59,996 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000867% 14/1,613,844 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,999
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00134%	74,878
European (non-Finnish)	0.000508%	196,661

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: COL7A1
Protein: p.Arg2685Pro
Coding: c.8054G>C
MANE Select: NM_000094
dbSNP: rs886058630
Type: single nucleotide variant
Location: chr3:48567183 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2685: the 'triple-helical region' region; the 'disordered' region

Full COL7A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa dystrophica — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COL7A1 p.Arg2685Ter Pathogenic ★★ same residue
COL7A1 p.Arg2685Gln Uncertain significance ★ same residue
COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2587+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2587+40G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.266+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2710+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2992+2T>G 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/col7a1-p-arg2685pro (accessed [today's date]).

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