CA4 p.Ala164=
c.492G>A · rs139119204 · VCV596737
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.845%, afr)
Conditions
1
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 -10 | GERP -3.3 |
| Overall | ||
| CADD | 0.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.845%
African / African-American · 634/75,046 alleles
Filtering AF
0.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.769%
Overall
0.0476%
768/1,613,668 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.845% | 118 |
| Admixed American | 0.0883% | 1,133 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0576% | 1,736 |
| South Asian | 0.0176% | 5,693 |
| East Asian | 0.00891% | 11,218 |
| European (non-Finnish) | 0.00178% | 56,169 |
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.Ala164=
- Coding
- c.492G>A
- MANE Select
- NM_000717
- dbSNP
- rs139119204
- Type
- single nucleotide variant
- Location
- chr17:60157767 (GRCh38)
- Gene constraint
- LOEUF 0.975 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.86 · 10 PDB
- Residue 164
- a disulfide bond; the alpha-carbonic anhydrase domain; a β-strand
Similar variants
- CA4 p.Asp268Asn Uncertain significance ★★ ⚠ same condition
- CA4 p.Asn177Lys Benign/Likely benign ★★ ⚠ same condition
- CA4 p.Asp161= Likely benign ★★ same condition
- CA4 p.Lys145= Benign/Likely benign ★★ same condition
- CA4 p.Pro287= Benign/Likely benign ★★ same condition
- CA4 p.Ser119= Benign/Likely benign ★★ same condition
- CA4 p.Cys229Ter Likely pathogenic ★ same condition
- CA4 p.Ter313Arg Likely pathogenic ★ 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-ala164 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown