SCAF4 p.Pro953=
c.2859G>A · VCV4887239
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.177%, afr)
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 -3.9 | GERP -4.3 |
| Overall | ||
| CADD | 6.123 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.177%
African / African-American · 133/74,942 alleles
Filtering AF
0.153%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.144%
Overall
0.0119%
192/1,611,408 alleles · rare
exomes 105/1,459,232 · genomes 87/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.177% | 563 |
| Admixed American | 0.01% | 9,990 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,807 |
| European (non-Finnish) | 0.00416% | 24,041 |
| East Asian | 0.00223% | 44,834 |
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
- SCAF4
- Protein
- p.Pro953=
- Coding
- c.2859G>A
- MANE Select
- NM_020706
- Type
- single nucleotide variant
- Location
- chr21:31671984 (GRCh38)
- Gene constraint
- LOEUF 0.285 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.53 · 1 PDB
- Residue 953
- a UniProt-annotated variant site (in fzs; likely pathogenic); the 'disordered' region
Similar variants
- SCAF4 p.Pro953Leu Uncertain significance ★ ⚠ same residue
- SCAF4 p.Arg447Ter Pathogenic ★★ same type
- SCAF4 p.Arg475Ter Pathogenic ★★ same type
- SCAF4 p.Arg477Ter Pathogenic ★★ same type
- SCAF4 p.Arg491Ter Pathogenic/Likely pathogenic ★★ same type
- SOD1 p.Gly73Ser Likely pathogenic ★★ same type
- SCAF4 p.Arg71Gln Uncertain significance ★★ ⚠ same type
- SCAF4 p.Asn627Ser 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/scaf4-p-pro953 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown