Is COL7A1 c.4635+1G>A pathogenic?

COL7A1 c.4635+1G>A is classified Pathogenic/Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-22). Very rare (popmax 0.0011%, sas); Associated with transient bullous dermolysis of the newborn.

What condition is associated with COL7A1 c.4635+1G>A?

COL7A1 c.4635+1G>A is associated with transient bullous dermolysis of the newborn, recessive dystrophic epidermolysis bullosa (ClinVar).

How common is COL7A1 c.4635+1G>A in the general population?

COL7A1 c.4635+1G>A is very rare (popmax 0.0011%, sas) (gnomAD).

COL7A1 c.4635+1G>A

Q: How is Self-improving dystrophic epidermolysis bullosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs774890570 · VCV1685661

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

transient bullous dermolysis of the newborn

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.97	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.82	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3	GERP 2, phastCons 1
Non-coding constraint	Z 3.45	1 kb window · o/e 0.78 · regional · uncalibrated
Overall
CADD	28.8	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 0.0011% South Asian · 1/91,088 alleles

Overall 6.84e-05% 1/1,461,700 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
Coding: c.4635+1G>A
MANE Select: NM_000094
dbSNP: rs774890570
Type: single nucleotide variant
Location: chr3:48582322 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)

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

Disease context

transient bullous dermolysis of the newborn — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: recessive dystrophic epidermolysis bullosa

For Self-improving dystrophic epidermolysis bullosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
COL7A1 c.2993-2A>G 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-c-4635-plus-1g-a (accessed [today's date]).

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