CA4 p.Lys145=
c.435A>G · rs201241903 · VCV891580
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.189%, eas)
Conditions
2
inherited retinal dystrophy
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 0.46 | GERP -2.7, phastCons 0.025 |
| Overall | ||
| CADD | 5.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.189%
East Asian · 85/44,880 alleles
Filtering AF
0.157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.145%
Overall
0.00533%
86/1,614,080 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.189% | 528 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
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.Lys145=
- Coding
- c.435A>G
- MANE Select
- NM_000717
- dbSNP
- rs201241903
- Type
- single nucleotide variant
- Location
- chr17:60157710 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 145
- a disulfide bond; the alpha-carbonic anhydrase domain; a β-strand
Similar variants
- CA4 p.Asp268Asn Uncertain significance ★★ ⚠ same condition
- CA4 p.Ile54Met Uncertain significance ★★ ⚠ same condition
- CA4 p.Phe70Leu Uncertain significance ★★ ⚠ same condition
- CA4 c.-24G>C Benign ★★ same condition
- CA4 c.-47C>G Benign ★★ same condition
- CA4 p.Ala164= Benign/Likely benign ★★ same condition
- CA4 p.Arg239Gln Benign ★★ same condition
- CA4 p.Asn177Lys Benign/Likely benign ★★ same condition
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-lys145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown