COL4A4 p.Pro99=
c.297T>A · rs1576662029 · VCV666680
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
hematuria, benign familial
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 0.62 | GERP -1.2, phastCons 0.003 |
| Overall | ||
| CADD | 7.341 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,020 alleles
Overall
6.84e-05%
1/1,461,878 alleles · very rare
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.Pro99=
- Coding
- c.297T>A
- MANE Select
- NM_000092
- dbSNP
- rs1576662029
- Type
- single nucleotide variant
- Location
- chr2:227121044 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 99
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL4A4 p.Pro99fs Pathogenic/Likely pathogenic ★★ same residue
- COL4A4 c.1030-2A>C Likely pathogenic ★★ same condition
- COL4A4 c.1099+1G>T Pathogenic/Likely pathogenic ★★ same condition
- COL4A4 c.1369+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL4A4 c.1459+1G>A Pathogenic ★★ same condition
- COL4A4 c.1696+1G>A Likely pathogenic ★★ same condition
- COL4A4 c.1696+1G>T Likely pathogenic ★★ same condition
- COL4A4 c.1697-1G>A Pathogenic/Likely 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/col4a4-p-pro99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown