COL8A2 p.Lys99=
c.297A>G · rs759570892 · VCV1599957
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0348%, mid)
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 0.79 | GERP 0.76, phastCons 1 |
| Overall | ||
| CADD | 7.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0348%
Middle Eastern · 2/5,754 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0278%
Overall
0.0249%
390/1,564,820 alleles · ultra-rare
exomes 349/1,414,646 · genomes 41/150,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0348% | 2,877 |
| European (non-Finnish) | 0.0316% | 3,166 |
| Finnishnot grpmax-eligible | 0.0128% | 7,801 |
| Remaining individualsnot grpmax-eligible | 0.00988% | 10,117 |
| African / African-American | 0.0068% | 14,706 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0035% | 28,542 |
| East Asian | 0.00231% | 43,230 |
| Admixed American | 0.00188% | 53,062 |
| South Asian | 0.00117% | 85,646 |
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.Lys99=
- Coding
- c.297A>G
- MANE Select
- NM_005202
- dbSNP
- rs759570892
- Type
- single nucleotide variant
- Location
- chr1:36099384 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.03
- Residue 99
- the 'disordered' region; the 'triple-helical region' 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-lys99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown