COL4A6 p.Pro641=
c.1923G>A · VCV4751563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, mid)
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 -0.13 | GERP -3.4, phastCons 0.88 |
| Overall | ||
| CADD | 0.287 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
Middle Eastern · 1/4,161 alleles
Filtering AF
0.00142%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000695%
Overall
0.00128%
15/1,170,939 alleles · ultra-rare
exomes 11/1,060,403 · genomes 4/110,536 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.024% | 4,161 |
| African / African-American | 0.00537% | 18,639 |
| Admixed American | 0.00231% | 43,268 |
| European (non-Finnish) | 0.00115% | 87,184 |
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
- COL4A6
- Protein
- p.Pro641=
- Coding
- c.1923G>A
- MANE Select
- NM_033641
- Type
- single nucleotide variant
- Location
- chrX:108187124 (GRCh38)
- Structure
- AlphaFold pLDDT 48.27
- Residue 641
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A6 p.Pro641Leu Benign/Likely benign ★★ ⚠ same residue
- COL4A6 c.3970+5G>A Uncertain significance ★★ same type
- COL4A6 p.Ala1275Thr Uncertain significance ★★ ⚠ same type
- COL4A6 p.Ala398Ser Uncertain significance ★★ ⚠ same type
- COL4A6 p.Ala421Gly Uncertain significance ★★ ⚠ same type
- COL4A6 p.Ala748Val Uncertain significance ★★ ⚠ same type
- COL4A6 p.Ala886Thr Uncertain significance ★★ ⚠ same type
- COL4A6 p.Arg1025Trp 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/col4a6-p-pro641 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown