CA4 p.Lys60=
c.180G>A · rs111561872 · VCV741529
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.513%, afr)
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 3.8 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 4.495 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.513%
African / African-American · 385/75,052 alleles
Filtering AF
0.471%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.454%
Overall
0.0279%
450/1,613,880 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.513% | 195 |
| Remaining individualsnot grpmax-eligible | 0.0768% | 1,302 |
| Middle Eastern | 0.066% | 1,516 |
| Admixed American | 0.00833% | 12,006 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.000593% | 168,533 |
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.Lys60=
- Coding
- c.180G>A
- MANE Select
- NM_000717
- dbSNP
- rs111561872
- Type
- single nucleotide variant
- Location
- chr17:60156627 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 60
- 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-lys60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown