COL4A1 p.Pro654=
c.1962G>A · rs375980154 · VCV1879262
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -20 | GERP -2.9 |
| Overall | ||
| CADD | 0.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000868%
14/1,613,732 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| South Asian | 0.00439% | 22,767 |
| Admixed American | 0.00333% | 29,999 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,446 |
| European (non-Finnish) | 0.000424% | 236,001 |
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
- COL4A1
- Protein
- p.Pro654=
- Coding
- c.1962G>A
- MANE Select
- NM_001845
- dbSNP
- rs375980154
- Type
- single nucleotide variant
- Location
- chr13:110183212 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.43 · 4 PDB
- Residue 654
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A1 p.Pro654Leu Uncertain significance ★★ ⚠ same residue
- COL4A1 c.1085-2A>G Likely pathogenic ★★ same type
- COL4A1 c.1991-2A>G Likely pathogenic ★★ same type
- COL4A1 c.2458+1G>A Pathogenic ★★ same type
- COL4A1 c.2458+2T>C Pathogenic/Likely pathogenic ★★ same type
- COL4A1 c.3742+1G>A Pathogenic ★★ same type
- COL4A1 c.388-1G>C Pathogenic/Likely pathogenic ★★ same type
- COL4A1 c.4150+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/col4a1-p-pro654 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown