Is COL7A1 p.Pro1699= (c.5097G>A) pathogenic?

COL7A1 p.Pro1699= (c.5097G>A) is classified Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-15). Very rare (popmax 0.00866%, nfe); Associated with epidermolysis bullosa with congenital localized absence of skin and deformity of nails.

What condition is associated with COL7A1 p.Pro1699= (c.5097G>A)?

COL7A1 p.Pro1699= (c.5097G>A) is associated with epidermolysis bullosa with congenital localized absence of skin and deformity of nails, transient bullous dermolysis of the newborn, generalized dominant dystrophic epidermolysis bullosa (ClinVar).

How common is COL7A1 p.Pro1699= (c.5097G>A) in the general population?

COL7A1 p.Pro1699= (c.5097G>A) is very rare (popmax 0.00866%, nfe) (gnomAD).

COL7A1 p.Pro1699=

c.5097G>A · rs369034739 · VCV631925

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00866%, nfe)

Conditions

epidermolysis bullosa with congenital localized absence of skin and deformity of nails

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss, 39 bp away · masked 0 · deltas
Pangolin	Δ0.26	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6.9	GERP -4.4
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00866% European (non-Finnish) · 102/1,178,044 alleles

Filtering AF 0.00725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00677%

Overall 0.00677% 109/1,609,724 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00866%	11,549
Admixed American	0.00671%	14,894
Remaining individualsnot grpmax-eligible	0.00321%	31,145
East Asian	0.00223%	44,774

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.Pro1699=
Coding: c.5097G>A
MANE Select: NM_000094
dbSNP: rs369034739
Type: single nucleotide variant
Location: chr3:48580300 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 1699: the 'disordered' region; the 'triple-helical region' region

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

Disease context

epidermolysis bullosa with congenital localized absence of skin and deformity of nails — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: transient bullous dermolysis of the newborn generalized dominant dystrophic epidermolysis bullosa pretibial dystrophic epidermolysis bullosa recessive dystrophic epidermolysis bullosa dystrophic epidermolysis bullosa pruriginosa nonsyndromic congenital nail disorder 8

Similar variants

COL7A1 p.Pro1699Leu Pathogenic/Likely pathogenic ★★ ⚠ 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
COL7A1 c.266+1G>A Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.266+2T>C 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-pro1699 (accessed [today's date]).

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