COL8A2 p.Ala114=
c.342T>A · VCV4966096
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00231%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -3.9 |
| Overall | ||
| CADD | 0.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00231%
European (non-Finnish) · 27/1,166,848 alleles
Filtering AF
0.00158%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00177%
28/1,582,218 alleles · very rare
exomes 28/1,430,938 · genomes 0/151,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00231% | 43,217 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,240 |
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.Ala114=
- Coding
- c.342T>A
- MANE Select
- NM_005202
- Type
- single nucleotide variant
- Location
- chr1:36099339 (GRCh38)
- Gene constraint
- LOEUF 1.139 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 58.03
- Residue 114
- the 'disordered' region; the 'triple-helical region' region
Similar variants
- COL8A2 p.Ala114Thr 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-ala114 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown