CSAD p.Ala199=
c.597G>A · rs80280748 · VCV778639
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.28%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.038 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.28 | GERP -2.4, phastCons 0.39 |
| Overall | ||
| CADD | 9.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.28%
African / African-American · 2,456/74,966 alleles
Filtering AF
3.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.12%
Overall
0.349%
5,630/1,613,972 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.28% | 31 |
| South Asian | 1.86% | 54 |
| Middle Eastern | 1.25% | 80 |
| Admixed American | 0.725% | 138 |
| Remaining individualsnot grpmax-eligible | 0.536% | 187 |
| Finnishnot grpmax-eligible | 0.167% | 598 |
| Ashkenazi Jewishnot grpmax-eligible | 0.122% | 822 |
| European (non-Finnish) | 0.041% | 2,438 |
| East Asian | 0.0223% | 4,487 |
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
- CSAD
- Protein
- p.Ala199=
- Coding
- c.597G>A
- MANE Select
- NM_001244705
- dbSNP
- rs80280748
- Type
- single nucleotide variant
- Location
- chr12:53170473 (GRCh38)
- Gene constraint
- LOEUF 0.972 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.67 · 1 PDB
- Residue 199
- an α-helix
Similar variants
- CSAD p.Ala103= Benign ★★ same type
- CSAD p.Glu50= Benign ★★ same type
- CSAD c.-21C>T Uncertain significance ★ same type
- CSAD c.-24G>T Uncertain significance ★ same type
- CSAD c.-27C>T Uncertain significance ★ same type
- CSAD c.-33C>G Uncertain significance ★ same type
- CSAD c.-48A>G Uncertain significance ★ same type
- CSAD c.-90-660A>G 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/csad-p-ala199 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown