CA2 p.Leu223=
c.667T>C · rs750229992 · VCV1561381
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -0.84 | GERP -3.4 |
| Overall | ||
| CADD | 0.472 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,872 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.000685%
10/1,460,704 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,479 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,820 |
| European (non-Finnish) | 8.48e-05% | 1,179,067 |
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
- CA2
- Protein
- p.Leu223=
- Coding
- c.667T>C
- MANE Select
- NM_000067
- dbSNP
- rs750229992
- Type
- single nucleotide variant
- Location
- chr8:85480673 (GRCh38)
- Gene constraint
- LOEUF 1.491 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.38 · 1249 PDB
- Residue 223
- the alpha-carbonic anhydrase domain; an α-helix
Similar variants
- CA2 c.232+1G>A Pathogenic ★★ same type
- CA2 p.Gln92Pro Likely pathogenic ★★ same type
- CA2 p.Glu204Ter Pathogenic/Likely pathogenic ★★ same type
- CA2 p.Tyr193Ter Likely pathogenic ★★ same type
- CA2 p.Arg181Cys Uncertain significance ★★ ⚠ same type
- CA2 p.Arg181His Uncertain significance ★★ ⚠ same type
- CA2 p.Arg226His Uncertain significance ★★ ⚠ same type
- CA2 p.Arg245Cys 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/ca2-p-leu223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown