SCP2 p.Pro408=
c.1224G>A · rs80253221 · VCV559027
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.35%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -5.9 | GERP -4.4 |
| Overall | ||
| CADD | 4.956 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.35%
African / African-American · 1,763/75,010 alleles
Filtering AF
2.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.22%
Overall
0.123%
1,987/1,614,078 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.35% | 43 |
| Remaining individualsnot grpmax-eligible | 0.173% | 579 |
| Admixed American | 0.103% | 968 |
| Middle Eastern | 0.0495% | 2,020 |
| South Asian | 0.0187% | 5,357 |
| European (non-Finnish) | 0.00288% | 34,706 |
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
- SCP2
- Protein
- p.Pro408=
- Coding
- c.1224G>A
- MANE Select
- NM_002979
- dbSNP
- rs80253221
- Type
- single nucleotide variant
- Location
- chr1:53015032 (GRCh38)
- Gene constraint
- LOEUF 0.944 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.39 · 2 PDB
Similar variants
- SCP2 c.825+1G>T Pathogenic/Likely pathogenic ★★ same type
- SCP2 p.Gln371Ter Pathogenic ★★ same type
- SCP2 p.Ala359Val Uncertain significance ★★ ⚠ same type
- SCP2 p.Ala427Gly Uncertain significance ★★ ⚠ same type
- SCP2 p.Ala46Val Uncertain significance ★★ ⚠ same type
- SCP2 p.Ala545Asp Uncertain significance ★★ same type
- SCP2 p.Arg105Cys Uncertain significance ★★ ⚠ same type
- SCP2 p.Arg13Gln 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/scp2-p-pro408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown