SCP2 p.Phe216=
c.648T>C · rs774694600 · VCV285845
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, sas)
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 0.095 | GERP 1.6, phastCons 0.94 |
| Overall | ||
| CADD | 7.774 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
South Asian · 34/89,592 alleles
Filtering AF
0.0278%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0244%
Overall
0.00336%
52/1,547,366 alleles · ultra-rare
exomes 49/1,395,158 · genomes 3/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0379% | 2,635 |
| Middle Eastern | 0.0337% | 2,966 |
| Admixed American | 0.0117% | 8,559 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,023 |
| European (non-Finnish) | 0.000536% | 186,666 |
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.Phe216=
- Coding
- c.648T>C
- MANE Select
- NM_002979
- dbSNP
- rs774694600
- Type
- single nucleotide variant
- Location
- chr1:52976743 (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-phe216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown