COL7A1 p.Pro331=
c.993G>A · rs200086083 · VCV1664019
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -3.4 |
| Overall | ||
| CADD | 2.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.00062%
10/1,613,542 alleles · ultra-rare
exomes 9/1,461,388 · genomes 1/152,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| African / African-American | 0.00267% | 37,446 |
| South Asian | 0.0022% | 45,538 |
| Admixed American | 0.00167% | 60,000 |
| European (non-Finnish) | 0.000339% | 295,010 |
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.Pro331=
- Coding
- c.993G>A
- MANE Select
- NM_000094
- dbSNP
- rs200086083
- Type
- single nucleotide variant
- Location
- chr3:48592451 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI <0.01 (gnomAD)
- Residue 331
- the 'nonhelical region (nc1)' region; the fibronectin type-iii 2 domain
Similar variants
- COL7A1 p.Pro331Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- COL7A1 c.1240+1G>T Likely pathogenic ★★ same type
- COL7A1 c.1637-1G>A Pathogenic/Likely pathogenic ★★ same type
- COL7A1 c.1906+1G>T Likely pathogenic ★★ same type
- COL7A1 c.2171-2A>G Likely pathogenic ★★ same type
- COL7A1 c.2587+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL7A1 c.2587+40G>A Pathogenic/Likely pathogenic ★★ same type
- COL7A1 c.266+1G>A Pathogenic/Likely pathogenic ★★ same type
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-pro331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown