COL4A6 p.Pro176=
c.528T>G · rs12390371 · VCV592972
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.926%, afr)
Conditions
1
hearing loss, X-linked 6
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 -4.3 | GERP -2.8 |
| Overall | ||
| CADD | 0.618 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.926%
African / African-American · 530/57,240 alleles
Filtering AF
0.861%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.835%
Overall
0.0496%
599/1,208,592 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.926% | 108 |
| Admixed American | 0.0678% | 1,475 |
| Remaining individualsnot grpmax-eligible | 0.0589% | 1,698 |
| Middle Eastern | 0.023% | 4,346 |
| South Asian | 0.00885% | 11,294 |
| European (non-Finnish) | 0.000447% | 223,566 |
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.Pro176=
- Coding
- c.528T>G
- MANE Select
- NM_033641
- dbSNP
- rs12390371
- Type
- single nucleotide variant
- Location
- chrX:108209987 (GRCh38)
- Structure
- AlphaFold pLDDT 48.27
- Residue 176
- the 'triple-helical region' region; the 'disordered' region
Similar variants
- COL4A6 p.Arg1269Ter Uncertain significance ★★ same condition
- COL4A6 p.Gly1484Arg Uncertain significance ★★ ⚠ same condition
- COL4A6 c.2132-6G>A Benign/Likely benign ★★ same condition
- COL4A6 c.2132-6G>T Benign/Likely benign ★★ same condition
- COL4A6 c.2956+39G>A Benign ★★ same condition
- COL4A6 c.3138+17C>T Benign/Likely benign ★★ same condition
- COL4A6 c.3139-4G>A Benign/Likely benign ★★ same condition
- COL4A6 c.3809-14G>A Benign/Likely benign ★★ same condition
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-pro176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown