CA2 c.232+1G>A
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +1 | canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone |
| SpliceAI | Δ1.00 | donor loss · deltas |
| Pangolin | Δ0.87 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.8, phastCons 1 |
| Non-coding constraint | Z 0.44 | 1 kb window · o/e 0.97 · regional · uncalibrated |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,821 |
| Admixed Americangrpmax | 0.00334% | 29,909 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- Coding
- c.232+1G>A
- MANE Select
- NM_000067
- dbSNP
- rs573750741
- Type
- single nucleotide variant
- Location
- chr8:85465470 (GRCh38)
- Gene constraint
- LOEUF 1.491 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 97.38 · 1249 PDB
Disease context
autosomal recessive osteopetrosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: osteopetrosis
For Osteopetrosis with renal tubular acidosis (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- CA2 p.Gln92Pro Likely pathogenic ★★ same condition
- CA2 p.Glu204Ter Pathogenic/Likely pathogenic ★★ same condition
- CA2 p.Tyr193Ter Likely pathogenic ★★ same condition
- CA2 p.Arg181Cys Uncertain significance ★★ ⚠ same condition
- CA2 p.Arg181His Uncertain significance ★★ ⚠ same condition
- CA2 p.Arg226His Uncertain significance ★★ ⚠ same condition
- CA2 p.Asn67Asp Uncertain significance ★★ ⚠ same condition
- CA2 p.Glu14Lys Uncertain significance ★★ ⚠ same condition
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-c-232-plus-1g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown