CA2 p.Ala141=
c.423C>T · VCV3605636
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
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 0.047 | GERP -0.65, phastCons 0.97 |
| Overall | ||
| CADD | 12.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,078 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00136%
22/1,613,578 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,108 |
| African / African-American | 0.00667% | 15,003 |
| Admixed American | 0.00333% | 30,005 |
| East Asian | 0.00223% | 44,868 |
| European (non-Finnish) | 0.000339% | 294,884 |
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.Ala141=
- Coding
- c.423C>T
- MANE Select
- NM_000067
- Type
- single nucleotide variant
- Location
- chr8:85474395 (GRCh38)
- Gene constraint
- LOEUF 1.491 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.38 · 1249 PDB
- Residue 141
- the alpha-carbonic anhydrase domain; a β-strand
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-ala141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown