CA2 p.Lys227=
c.681A>G · rs191570649 · VCV770381
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0454%, nfe)
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 -4.2 | GERP -3.7 |
| Overall | ||
| CADD | 0.325 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0454%
European (non-Finnish) · 536/1,179,656 alleles
Filtering AF
0.0422%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.041%
Overall
0.0341%
550/1,613,692 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0454% | 2,201 |
| Admixed American | 0.0117% | 8,567 |
| African / African-American | 0.00533% | 18,758 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
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.Lys227=
- Coding
- c.681A>G
- MANE Select
- NM_000067
- dbSNP
- rs191570649
- Type
- single nucleotide variant
- Location
- chr8:85480687 (GRCh38)
- Gene constraint
- LOEUF 1.491 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.38 · 1249 PDB
- Residue 227
- the alpha-carbonic anhydrase domain; a turn
Similar variants
- CA2 p.Lys227fs Pathogenic/Likely pathogenic ★★ same residue
- 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
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-lys227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown