CA4 p.Tyr75=
c.225C>T · rs146160539 · VCV1168012
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.932%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -7.2 | GERP -4 |
| Overall | ||
| CADD | 2.253 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.932%
African / African-American · 699/75,038 alleles
Filtering AF
0.874%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.851%
Overall
0.0491%
792/1,614,050 alleles · rare
exomes 401/1,461,744 · genomes 391/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.932% | 107 |
| Remaining individualsnot grpmax-eligible | 0.0448% | 2,232 |
| Admixed American | 0.0416% | 2,401 |
| Middle Eastern | 0.0165% | 6,062 |
| Finnishnot grpmax-eligible | 0.0109% | 9,145 |
| East Asian | 0.00446% | 22,435 |
| South Asian | 0.00439% | 22,770 |
| European (non-Finnish) | 0.0022% | 45,382 |
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.Tyr75=
- Coding
- c.225C>T
- MANE Select
- NM_000717
- dbSNP
- rs146160539
- Type
- single nucleotide variant
- Location
- chr17:60156672 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 75
- a β-strand; 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-tyr75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown