CA4 p.Leu130=
c.390C>T · rs772123429 · VCV1124059
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, 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 -9.7 | GERP -3.3 |
| Overall | ||
| CADD | 0.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,090 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00192%
28/1,461,886 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,545 |
| European (non-Finnish) | 0.00212% | 47,201 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,508 |
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.Leu130=
- Coding
- c.390C>T
- MANE Select
- NM_000717
- dbSNP
- rs772123429
- Type
- single nucleotide variant
- Location
- chr17:60157548 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 130
- a disulfide bond; the alpha-carbonic anhydrase domain; a β-strand
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-leu130 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown