COL4A4 p.Pro863=
c.2589C>T · rs772517977 · VCV594726
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00878%, sas)
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 0.14 | GERP -4, phastCons 0.22 |
| Overall | ||
| CADD | 8.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00878%
South Asian · 8/91,076 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00312%
Overall
0.00366%
59/1,613,910 alleles · very rare
exomes 52/1,461,828 · genomes 7/152,082 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00878% | 11,385 |
| African / African-American | 0.00801% | 12,482 |
| European (non-Finnish) | 0.00356% | 28,095 |
| East Asian | 0.00223% | 44,880 |
| Admixed American | 0.00167% | 60,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
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.Pro863=
- Coding
- c.2589C>T
- MANE Select
- NM_000092
- dbSNP
- rs772517977
- Type
- single nucleotide variant
- Location
- chr2:227056072 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 863
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A4 p.Pro863His Uncertain significance ★ ⚠ 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
- COL4A4 c.1459+1G>A Pathogenic ★★ same type
- COL4A4 c.1623+5G>T 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-pro863 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown