COL4A4 p.Pro222=
c.666G>A · rs111945121 · VCV447193
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 14 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.25%, afr)
Conditions
2
kidney disorder
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 -8.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.25%
African / African-American · 1,689/74,938 alleles
Filtering AF
2.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.13%
Overall
0.13%
2,097/1,611,676 alleles · low-frequency
exomes 1,138/1,459,538 · genomes 959/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.25% | 44 |
| Remaining individualsnot grpmax-eligible | 0.237% | 422 |
| Middle Eastern | 0.181% | 551 |
| Admixed American | 0.142% | 704 |
| Finnishnot grpmax-eligible | 0.072% | 1,389 |
| South Asian | 0.011% | 9,062 |
| European (non-Finnish) | 0.00916% | 10,913 |
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.Pro222=
- Coding
- c.666G>A
- MANE Select
- NM_000092
- dbSNP
- rs111945121
- Type
- single nucleotide variant
- Location
- chr2:227108860 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 222
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A4 p.Pro222Leu Likely benign ★★ same residue
- COL4A4 p.Pro222Ser Uncertain significance ★ ⚠ same residue
- COL4A4 c.1030-2A>C Likely pathogenic ★★ same condition
- COL4A4 c.1369+1G>A Pathogenic/Likely pathogenic ★★ same condition
- COL4A4 c.1370-2A>C Likely 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-pro222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown