SCO2 p.Ala259=
c.777G>A · rs375632322 · VCV2046423
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0337%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not looked up on this page · why |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -4 |
| Overall | ||
| CADD | 0.352 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0337%
Middle Eastern · 2/5,928 alleles
Filtering AF
0.00751%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00593%
Overall
0.00366%
59/1,613,732 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0337% | 2,964 |
| South Asian | 0.0132% | 7,590 |
| Admixed American | 0.00833% | 12,004 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| East Asian | 0.00446% | 22,442 |
| African / African-American | 0.004% | 25,016 |
| European (non-Finnish) | 0.00263% | 38,066 |
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
- SCO2
- Protein
- p.Ala259=
- Coding
- c.777G>A
- MANE Select
- NM_152299 · reported on NM_005138
- dbSNP
- rs375632322
- Type
- single nucleotide variant
- Location
- chr22:50523635 (GRCh38)
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/sco2-p-ala259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown