COL4A4 p.Pro1330=
c.3990G>A · rs62189848 · VCV765414
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, eas)
Conditions
1
Inborn genetic diseases
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 -14 | GERP -3.6 |
| Overall | ||
| CADD | 0.228 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
East Asian · 9/44,848 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0078%
Overall
0.00149%
24/1,611,566 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0201% | 4,983 |
| South Asian | 0.0132% | 7,572 |
| European (non-Finnish) | 0.000255% | 392,821 |
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.Pro1330=
- Coding
- c.3990G>A
- MANE Select
- NM_000092
- dbSNP
- rs62189848
- Type
- single nucleotide variant
- Location
- chr2:227027993 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 1330
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A4 p.Pro1330Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- COL4A4 p.Arg349Ter Pathogenic/Likely pathogenic ★★ same condition
- COL4A4 p.Cys1588Ser Likely pathogenic ★★ same condition
- COL4A4 c.4522+6G>A Uncertain significance ★★ same condition
- COL4A4 p.Ala1546Thr Uncertain significance ★★ ⚠ same condition
- COL4A4 p.Arg1565Cys Uncertain significance ★★ ⚠ same condition
- COL4A4 p.Arg641Gln Uncertain significance ★★ ⚠ same condition
- COL4A4 p.Arg811Thr Uncertain significance ★★ ⚠ 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-pro1330 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown