COL8A2 p.Ala441=
c.1323A>G · rs182708720 · VCV1599098
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.06%, afr)
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 0.18 | GERP -1.2, phastCons 0.97 |
| Overall | ||
| CADD | 6.662 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.06%
African / African-American · 1,504/73,108 alleles
Filtering AF
1.97%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.94%
Overall
0.11%
1,711/1,551,714 alleles · low-frequency
exomes 802/1,399,868 · genomes 909/151,846 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.06% | 49 |
| Admixed American | 0.172% | 582 |
| Remaining individualsnot grpmax-eligible | 0.127% | 790 |
| Middle Eastern | 0.0385% | 2,599 |
| European (non-Finnish) | 0.0034% | 29,437 |
| South Asian | 0.00119% | 84,224 |
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
- COL8A2
- Protein
- p.Ala441=
- Coding
- c.1323A>G
- MANE Select
- NM_005202
- dbSNP
- rs182708720
- Type
- single nucleotide variant
- Location
- chr1:36098358 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.03
- Residue 441
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL8A2 p.Ala441Thr Uncertain significance ★ ⚠ same residue
- COL8A2 p.Arg149Gln Uncertain significance ★★ ⚠ same type
- COL8A2 p.Arg263Ser Uncertain significance ★★ ⚠ same type
- COL8A2 p.Arg372Cys Uncertain significance ★★ ⚠ same type
- COL8A2 p.Glu568Lys Uncertain significance ★★ ⚠ same type
- COL8A2 p.Gly549Ser Uncertain significance ★★ ⚠ same type
- COL8A2 p.Gly550Ser Uncertain significance ★★ ⚠ same type
- COL8A2 p.Gly559Glu 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/col8a2-p-ala441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown