COL4A2 p.Asp519=
c.1557C>T · rs781646506 · VCV932541
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00225%, eas)
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 -1.2 | GERP -0.66, phastCons 0.001 |
| Overall | ||
| CADD | 2.802 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00225%
East Asian · 1/44,508 alleles
Filtering AF
0.000768%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000609%
Overall
0.00113%
18/1,597,780 alleles · very rare
exomes 18/1,445,508 · genomes 0/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00225% | 44,508 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,686 |
| European (non-Finnish) | 0.00128% | 78,145 |
| South Asian | 0.00112% | 89,040 |
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
- COL4A2
- Protein
- p.Asp519=
- Coding
- c.1557C>T
- MANE Select
- NM_001846
- dbSNP
- rs781646506
- Type
- single nucleotide variant
- Location
- chr13:110458895 (GRCh38)
- Gene constraint
- LOEUF 0.618 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 47.97 · 4 PDB
- Residue 519
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A2 c.361-1G>A Pathogenic/Likely pathogenic ★★ same type
- COL4A2 p.Gly1389Arg Pathogenic/Likely pathogenic ★★ same type
- COL4A2 p.Gly619Asp Likely pathogenic ★★ same type
- COL4A2 c.2425+3G>A Uncertain significance ★★ same type
- COL4A2 c.315+5G>A Uncertain significance ★★ same type
- COL4A2 c.726+4A>G Uncertain significance ★★ same type
- COL4A2 p.Ala1183Val Uncertain significance ★★ ⚠ same type
- COL4A2 p.Ala1363Val Uncertain significance ★★ ⚠ 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/col4a2-p-asp519 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown