Is COL7A1 p.Ser73= (c.219T>C) pathogenic?

COL7A1 p.Ser73= (c.219T>C) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-02). Very rare (popmax 0.000678%, nfe); Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Ser73= (c.219T>C)?

COL7A1 p.Ser73= (c.219T>C) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Ser73= (c.219T>C) in the general population?

COL7A1 p.Ser73= (c.219T>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

COL7A1 p.Ser73=

c.219T>C · rs762065822 · VCV899902

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

epidermolysis bullosa dystrophica

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 -0.27	GERP -4
Overall
CADD	7.678	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,026 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,611,786 alleles · very rare exomes 7/1,459,568 · genomes 1/152,218 · 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: COL7A1
Protein: p.Ser73=
Coding: c.219T>C
MANE Select: NM_000094
dbSNP: rs762065822
Type: single nucleotide variant
Location: chr3:48594415 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 73: the 'nonhelical region (nc1)' region; the vwfa 1 domain

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 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
COL7A1 c.2993-2A>G Likely pathogenic ★★ same condition
COL7A1 c.3139+1G>A 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/col7a1-p-ser73 (accessed [today's date]).

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