CA4 p.Thr80=
c.240G>A · rs745408279 · VCV1662718
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -0.91 | GERP -4 |
| Overall | ||
| CADD | 1.946 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00186%
30/1,614,048 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| Admixed American | 0.00667% | 15,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| South Asian | 0.00329% | 30,363 |
| East Asian | 0.00223% | 44,888 |
| European (non-Finnish) | 0.00136% | 73,752 |
| African / African-American | 0.00133% | 74,922 |
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.Thr80=
- Coding
- c.240G>A
- MANE Select
- NM_000717
- dbSNP
- rs745408279
- Type
- single nucleotide variant
- Location
- chr17:60156687 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 80
- a disulfide bond; the alpha-carbonic anhydrase domain
Similar variants
- CA4 p.Thr80Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-thr80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown