COL4A4 p.Pro221=
c.663T>C · rs2475788588 · VCV2133002
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,611,760)
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 2.9 | GERP 0.63, phastCons 1 |
| Overall | ||
| CADD | 8.288 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,611,760). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- COL4A4
- Protein
- p.Pro221=
- Coding
- c.663T>C
- MANE Select
- NM_000092
- dbSNP
- rs2475788588
- Type
- single nucleotide variant
- Location
- chr2:227108863 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 221
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A4 p.Pro221Ser Uncertain significance ★★ ⚠ same residue
- COL4A4 p.Pro221fs 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
- COL4A4 c.1459+1G>A 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-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown