Is COL7A1 p.Arg20Ter (c.58C>T) pathogenic?

COL7A1 p.Arg20Ter (c.58C>T) is classified Pathogenic/Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-20). Very rare (popmax 0.000174%, nfe); Associated with pretibial dystrophic epidermolysis bullosa.

What condition is associated with COL7A1 p.Arg20Ter (c.58C>T)?

COL7A1 p.Arg20Ter (c.58C>T) is associated with pretibial dystrophic epidermolysis bullosa, transient bullous dermolysis of the newborn, generalized dominant dystrophic epidermolysis bullosa (ClinVar).

How common is COL7A1 p.Arg20Ter (c.58C>T) in the general population?

COL7A1 p.Arg20Ter (c.58C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

COL7A1 p.Arg20Ter

c.58C>T · rs886039562 · VCV265469

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

pretibial dystrophic epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 119
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -3.2
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,148,770 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000214% 3/1,401,272 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00171%	58,616
European (non-Finnish)grpmax	0.000174%	574,386

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg20Ter
Coding: c.58C>T
MANE Select: NM_000094
dbSNP: rs886039562
Type: single nucleotide variant
Location: chr3:48595102 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 20: the 'nonhelical region (nc1)' region

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

Disease context

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

Also linked: transient bullous dermolysis of the newborn generalized dominant dystrophic epidermolysis bullosa epidermolysis bullosa with congenital localized absence of skin and deformity of nails recessive dystrophic epidermolysis bullosa dystrophic epidermolysis bullosa pruriginosa nonsyndromic congenital nail disorder 8

Similar variants

COL7A1 p.Arg20fs Pathogenic ★★ same residue
COL7A1 p.Arg20Gln Uncertain significance ★ ⚠ same residue
COL7A1 p.Arg20Pro Conflicting classifications of pathogenicity ★ same residue
COL7A1 c.1240+1G>T Likely pathogenic ★★ same condition
COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.1906+1G>T Likely pathogenic ★★ same condition
COL7A1 c.2171-2A>G Likely pathogenic ★★ same condition
COL7A1 c.2587+1G>A 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/col7a1-p-arg20ter (accessed [today's date]).

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