Is COL7A1 p.Val2448= (c.7344G>A) pathogenic?

COL7A1 p.Val2448= (c.7344G>A) is classified Pathogenic/Likely pathogenic in COL7A1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-11-04). Very rare (popmax 0.00664%, nfe); Associated with pretibial dystrophic epidermolysis bullosa.

How common is COL7A1 p.Val2448= (c.7344G>A) in the general population?

COL7A1 p.Val2448= (c.7344G>A) is very rare (popmax 0.00664%, nfe) (gnomAD).

COL7A1 p.Val2448=

Q: What condition is associated with COL7A1 p.Val2448= (c.7344G>A)?

COL7A1 p.Val2448= (c.7344G>A) is associated with pretibial dystrophic epidermolysis bullosa, epidermolysis bullosa dystrophica, transient bullous dermolysis of the newborn (ClinVar).

c.7344G>A · rs201728948 · VCV372349

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00664%, nfe)

Conditions

pretibial dystrophic epidermolysis bullosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.63	donor gain · deltas
Pangolin	Δ0.47	gain · loss 0.42 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.78	GERP 0.52, phastCons 0.22
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00664% European (non-Finnish) · 78/1,174,990 alleles

Filtering AF 0.0054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.005%

Overall 0.00511% 82/1,604,474 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00664%	15,064
Remaining individualsnot grpmax-eligible	0.00484%	20,679
African / African-American	0.00134%	74,716

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.Val2448=
Coding: c.7344G>A
MANE Select: NM_000094
dbSNP: rs201728948
Type: single nucleotide variant
Location: chr3:48570639 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 2448: the 'triple-helical region' region; the 'disordered' 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: epidermolysis bullosa dystrophica 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 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.2587+40G>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-val2448 (accessed [today's date]).

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