CA4 p.Ala29=
c.87C>T · rs537429987 · VCV1154893
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, 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 0.033 | GERP 0.18 |
| Overall | ||
| CADD | 7.701 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,746 alleles
Filtering AF
0.00728%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00551%
Overall
0.00168%
27/1,611,378 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,392 |
| African / African-American | 0.0134% | 7,482 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,208 |
| European (non-Finnish) | 0.000679% | 147,357 |
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
- CA4
- Protein
- p.Ala29=
- Coding
- c.87C>T
- MANE Select
- NM_000717
- dbSNP
- rs537429987
- Type
- single nucleotide variant
- Location
- chr17:60155342 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 29
- a disulfide bond; an α-helix; the alpha-carbonic anhydrase domain
Similar variants
- CA4 c.745-9C>G Uncertain significance ★★ same type
- CA4 p.Ala156Val Uncertain significance ★★ ⚠ same type
- CA4 p.Ala308Ser Uncertain significance ★★ ⚠ same type
- CA4 p.Arg279Pro Uncertain significance ★★ ⚠ same type
- CA4 p.Arg50His Uncertain significance ★★ ⚠ same type
- CA4 p.Arg50Ser Uncertain significance ★★ ⚠ same type
- CA4 p.Asp131Asn Uncertain significance ★★ ⚠ same type
- CA4 p.Asp206Glu 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/ca4-p-ala29 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown