COL8A2 p.Ser588=
c.1764G>A · VCV3645494
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.197%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.80 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.79 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -7.1 | GERP -4.2 |
| Overall | ||
| CADD | 18.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.197%
Middle Eastern · 12/6,078 alleles
Filtering AF
0.114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0893%
Overall
0.0249%
401/1,611,706 alleles · rare
exomes 371/1,459,506 · genomes 30/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.197% | 507 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0574% | 1,741 |
| Remaining individualsnot grpmax-eligible | 0.0432% | 2,313 |
| Admixed American | 0.0367% | 2,726 |
| European (non-Finnish) | 0.0265% | 3,770 |
| East Asian | 0.0111% | 8,979 |
| South Asian | 0.00439% | 22,770 |
| African / African-American | 0.00133% | 74,930 |
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.Ser588=
- Coding
- c.1764G>A
- MANE Select
- NM_005202
- Type
- single nucleotide variant
- Location
- chr1:36097917 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.03
- Residue 588
- the c1q domain; the 'nonhelical region (nc1)' region
Similar variants
- 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
- COL8A2 p.Gly601Ala 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-ser588 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown