COL4A4 p.Arg97=
c.291C>T · rs749441530 · VCV255026
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0433%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.79 | GERP -4.7 |
| Overall | ||
| CADD | 2.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0433%
Admixed American · 26/59,994 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.026%
Overall
0.00248%
40/1,613,992 alleles · ultra-rare
exomes 36/1,461,866 · genomes 4/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0433% | 2,307 |
| South Asian | 0.00329% | 30,354 |
| African / African-American | 0.00267% | 37,459 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000678% | 147,504 |
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.Arg97=
- Coding
- c.291C>T
- MANE Select
- NM_000092
- dbSNP
- rs749441530
- Type
- single nucleotide variant
- Location
- chr2:227121050 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 97
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL4A4 p.Arg97His Uncertain significance ★★ ⚠ same residue
- COL4A4 p.Arg97Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg97 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown