COL4A4 p.Pro1515=
c.4545C>T · rs777758326 · VCV1138710
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, nfe)
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 -1.9 | GERP -3.6 |
| Overall | ||
| CADD | 3.731 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
European (non-Finnish) · 234/1,180,014 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0169%
Overall
0.0151%
244/1,614,068 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0198% | 5,043 |
| African / African-American | 0.00534% | 18,732 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| East Asian | 0.00223% | 44,902 |
| South Asian | 0.0022% | 45,545 |
| Admixed American | 0.00167% | 60,000 |
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
- COL4A4
- Protein
- p.Pro1515=
- Coding
- c.4545C>T
- MANE Select
- NM_000092
- dbSNP
- rs777758326
- Type
- single nucleotide variant
- Location
- chr2:227008282 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 1515
- the collagen iv nc1 domain; a disulfide bond; a β-strand
Similar variants
- COL4A4 p.Pro1515His Uncertain significance ★★ ⚠ same residue
- COL4A4 p.Pro1515Leu Uncertain significance ★ ⚠ same residue
- COL4A4 p.Pro1515fs Pathogenic/Likely pathogenic ★★ same residue
- COL4A4 c.1030-2A>C Likely pathogenic ★★ same type
- COL4A4 c.1099+1G>A Pathogenic ★★ same type
- COL4A4 c.1099+1G>T Pathogenic/Likely pathogenic ★★ same type
- COL4A4 c.1369+1G>A Pathogenic/Likely pathogenic ★★ same type
- COL4A4 c.1370-2A>C 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/col4a4-p-pro1515 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown