COL4A4 p.Pro46=
c.138T>C · rs183641557 · VCV2135829
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00153%, nfe)
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 0.23 | GERP -5.3, phastCons 0.5 |
| Overall | ||
| CADD | 1.184 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00153%
European (non-Finnish) · 18/1,179,962 alleles
Filtering AF
0.000953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00118%
19/1,614,094 alleles · very rare
exomes 18/1,461,794 · genomes 1/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00153% | 65,554 |
| African / African-American | 0.00133% | 75,054 |
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.Pro46=
- Coding
- c.138T>C
- MANE Select
- NM_000092
- dbSNP
- rs183641557
- Type
- single nucleotide variant
- Location
- chr2:227140215 (GRCh38)
- Gene constraint
- LOEUF 0.607 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 49.03 · 2 PDB
- Residue 46
- the '7s domain' region
Similar variants
- COL4A4 p.Pro46Thr 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
- COL4A4 c.1623+5G>T Likely 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-pro46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown