Is COL7A1 p.Pro2385fs (c.7154del) pathogenic?

COL7A1 p.Pro2385fs (c.7154del) is classified Pathogenic in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-03). Very rare (popmax 0.000254%, nfe).

How common is COL7A1 p.Pro2385fs (c.7154del) in the general population?

COL7A1 p.Pro2385fs (c.7154del) is very rare (popmax 0.000254%, nfe) (gnomAD).

COL7A1 p.Pro2385fs

c.7154del · rs909040709 · VCV1199942

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 94 of 119
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4, phastCons 0.003

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,916 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,630 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.Pro2385fs
Coding: c.7154del
MANE Select: NM_000094
dbSNP: rs909040709
Type: Deletion
Location: chr3:48571111 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2385: the 'triple-helical region' region; the 'disordered' region

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

Similar variants

COL7A1 p.Pro2385Ser Uncertain significance ★★ same residue
COL7A1 p.Pro2385= Likely benign ★ same residue
COL7A1 c.3832_3833del Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.4199del Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.4519-2del Likely pathogenic ★★ same type
COL7A1 c.4531_4564-42del Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.5304_5307+1del Pathogenic/Likely pathogenic ★★ same type
COL7A1 c.5389-2_5389-1del Likely pathogenic ★★ same type

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-pro2385fs (accessed [today's date]).

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