COL4A4 p.Pro730=
c.2190G>A · rs998610773 · VCV1101471
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Conditions
1
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 -3 | GERP -0.54 |
| Overall | ||
| CADD | 7.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,082 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00161%
26/1,613,916 alleles · very rare
exomes 25/1,461,802 · genomes 1/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,541 |
| European (non-Finnish) | 0.00195% | 51,305 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Pro730=
- Coding
- c.2190G>A
- MANE Select
- NM_000092
- dbSNP
- rs998610773
- Type
- single nucleotide variant
- Location
- chr2:227059598 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 730
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A4 p.Pro730Leu Uncertain significance ★★ ⚠ same residue
- COL4A4 p.Cys1480Ter Likely pathogenic ★★ same condition
- COL4A4 c.*2962A>G Uncertain significance ★★ same condition
- COL4A4 p.Ala1078Thr Benign/Likely benign ★★ same condition
- COL4A4 p.Ala401Val Benign/Likely benign ★★ same condition
- COL4A4 p.Asp1321= Benign/Likely benign ★★ same condition
- COL4A4 p.Glu1672= Benign/Likely benign ★★ same condition
- COL4A4 p.Glu594Gly Benign/Likely benign ★★ 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-pro730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown