CA8 p.Pro103=
c.309A>G · rs73685412 · VCV587857
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.433%, afr)
Conditions
1
Inborn genetic diseases
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 -5.5 | GERP -3.5 |
| Overall | ||
| CADD | 3.169 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.433%
African / African-American · 325/75,032 alleles
Filtering AF
0.394%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.379%
Overall
0.0229%
369/1,613,708 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.433% | 231 |
| Admixed American | 0.0317% | 3,159 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,166 |
| European (non-Finnish) | 0.000848% | 117,967 |
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
- CA8
- Protein
- p.Pro103=
- Coding
- c.309A>G
- MANE Select
- NM_004056
- dbSNP
- rs73685412
- Type
- single nucleotide variant
- Location
- chr8:60266033 (GRCh38)
- Gene constraint
- LOEUF 0.698 · pLI 0.24 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.51 · 1 PDB
- Residue 103
- the alpha-carbonic anhydrase domain
Similar variants
- CA8 p.Pro14Arg Uncertain significance ★★ ⚠ same condition
- CA8 p.Ser71Phe Uncertain significance ★★ ⚠ same condition
- CA8 c.576+5G>A Benign/Likely benign ★★ same condition
- CA8 p.Glu109= Benign ★★ same condition
- CA8 p.Glu22= Benign ★★ same condition
- CA8 p.Gly265= Benign/Likely benign ★★ same condition
- CA8 p.Leu112= Benign ★★ same condition
- CA8 p.Ser100Leu 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/ca8-p-pro103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown