COL7A1 p.Pro2145=
c.6435G>A · rs143458723 · VCV899581
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00768%, sas)
Conditions
1
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 1.5 | GERP -0.21, phastCons 1 |
| Overall | ||
| CADD | 10.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00768%
South Asian · 7/91,090 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00341%
55/1,613,966 alleles · very rare
exomes 45/1,461,744 · genomes 10/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00768% | 13,013 |
| African / African-American | 0.004% | 24,976 |
| European (non-Finnish) | 0.00356% | 28,096 |
| Admixed American | 0.00167% | 60,010 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| Finnishnot grpmax-eligible | 0.00156% | 63,924 |
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.Pro2145=
- Coding
- c.6435G>A
- MANE Select
- NM_000094
- dbSNP
- rs143458723
- Type
- single nucleotide variant
- Location
- chr3:48574509 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI <0.01 (gnomAD)
- Residue 2145
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL7A1 p.Pro2145Leu Uncertain significance ★★ same residue
- COL7A1 p.Pro2145Ser 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-pro2145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown