Is COL7A1 p.Asp149= (c.447C>T) pathogenic?

COL7A1 p.Asp149= (c.447C>T) is classified Conflicting classifications of pathogenicity in COL7A1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0164%, mid); Associated with epidermolysis bullosa dystrophica.

What condition is associated with COL7A1 p.Asp149= (c.447C>T)?

COL7A1 p.Asp149= (c.447C>T) is associated with epidermolysis bullosa dystrophica (ClinVar).

How common is COL7A1 p.Asp149= (c.447C>T) in the general population?

COL7A1 p.Asp149= (c.447C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

COL7A1 p.Asp149=

c.447C>T · rs372585819 · VCV903505

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

epidermolysis bullosa dystrophica

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -4.1
Overall
CADD	7.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00384% 62/1,613,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00801%	12,485
Remaining individualsnot grpmax-eligible	0.0064%	15,622
South Asian	0.00549%	18,216
East Asian	0.00446%	22,446
European (non-Finnish)	0.00373%	26,819

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.Asp149=
Coding: c.447C>T
MANE Select: NM_000094
dbSNP: rs372585819
Type: single nucleotide variant
Location: chr3:48593429 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Residue 149: 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.Asp149Asn Uncertain significance ★ ⚠ same residue
COL7A1 p.Asp149Glu Uncertain significance ★ same residue
COL7A1 c.1637-1G>A Pathogenic/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.2710+2T>C Pathogenic/Likely pathogenic ★★ same condition
COL7A1 c.2992+2T>G 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-asp149 (accessed [today's date]).

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