Is COL7A1 p.Ser47fs (c.139del) pathogenic?

COL7A1 p.Ser47fs (c.139del) is classified Pathogenic/Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-19). Very rare (popmax 0.00833%, amr); Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Ser47fs (c.139del)?

COL7A1 p.Ser47fs (c.139del) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Ser47fs (c.139del) in the general population?

COL7A1 p.Ser47fs (c.139del) is very rare (popmax 0.00833%, amr) (gnomAD).

COL7A1 p.Ser47fs

c.139del · rs1453568434 · VCV1968205

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

epidermolysis bullosa dystrophica

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 119
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
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 0.00833% Admixed American · 5/59,992 alleles

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

Overall 0.00031% 5/1,612,116 alleles · very rare

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.Ser47fs
Coding: c.139del
MANE Select: NM_000094
dbSNP: rs1453568434
Type: Deletion
Location: chr3:48594495 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 47: 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 p.Ser47= Uncertain significance same residue
COL7A1 c.3832_3833del Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.4519-2del Likely pathogenic ★★ same condition
COL7A1 c.5389-2_5389-1del Likely pathogenic ★★ same condition
COL7A1 c.5772+1del Pathogenic ★★ same condition
COL7A1 p.Ala121fs Pathogenic/Likely pathogenic ★★ same condition
COL7A1 p.Ala1503fs Pathogenic/Likely pathogenic ★★ same condition
COL7A1 p.Ala1517fs 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-ser47fs (accessed [today's date]).

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