COL8A2 p.Ala35=
c.105G>A · rs57985157 · VCV1249552
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 32%, eas) — too common for a highly-penetrant pathogenic allele
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 -1.5 | GERP -3 |
| Overall | ||
| CADD | 6.756 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32%
East Asian · 14,325/44,808 alleles
Filtering AF
31.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 31.4%
Overall
2.54%
40,921/1,612,446 alleles · common
exomes 34,871/1,460,264 · genomes 6,050/152,182 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 32% | 3 |
| Admixed American | 23.2% | 4 |
| Finnishnot grpmax-eligible | 3.52% | 28 |
| South Asian | 3.49% | 29 |
| Remaining individualsnot grpmax-eligible | 3.05% | 33 |
| African / African-American | 2.69% | 37 |
| Ashkenazi Jewishnot grpmax-eligible | 1.5% | 67 |
| Middle Eastern | 0.63% | 159 |
| European (non-Finnish) | 0.245% | 408 |
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.Ala35=
- Coding
- c.105G>A
- MANE Select
- NM_005202
- dbSNP
- rs57985157
- Type
- single nucleotide variant
- Location
- chr1:36100138 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.03
- Residue 35
- the 'nonhelical region (nc2)' region
Similar variants
- COL8A2 p.Ala35Val 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-ala35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown